RG2 glioma growth in rat cerebellum after subdural implantation

1986 ◽  
Vol 65 (2) ◽  
pp. 222-229 ◽  
Author(s):  
Stanislaw Krajewski ◽  
Jürgen C. W. Kiwit ◽  
Wolfgang Wechsler
Keyword(s):  
Light And Electron Microscopy ◽  
Tumor Model ◽  
Nerve Tissue ◽  
Blue Dye ◽  
Histological Techniques ◽  
Content Type ◽  
Rat Glioma ◽  
Glioma Growth ◽  
Microsurgical Techniques ◽  
Fine Print

✓ The nitrosourea-induced rat glioma clone RG2 was tested for its capacity to form multicellular tumor spheroids (MTS's). Resulting spheroids were investigated by light and electron microscopy with regard to their proliferation patterns and morphological features. Using microsurgical techniques and avoiding mechanical injury of the brain tissue, the authors successfully transplanted avascular MTS's under the dura of the cerebellum, above the vermis, in 43 adult syngeneic Fischer CD rats. The rate of tumor establishment was 93%, and the tumors that were solid and spheroid in shape grew exponentially. Neovascularization could be observed at 3 days after implantation, and invasion of the cerebellum occurred by 3 to 5 days. Neurological deterioration, including ataxia, impairment of walking, and apathy, could be observed after 10 days. The mean survival time was approximately 16 days. The subdural cerebellar tumors were studied by histological techniques, and two morphometric methods were applied to check the growth of implanted spheroids. All tumors were deeply stained with the Evans blue dye-albumin complex, demonstrating disturbance of the blood-brain barrier. The easy accessibility of the cerebellar vermis in rats, the microsurgical implantation of glioma spheroids under the dura avoiding nerve tissue disruption, and the high percentage of reproducible establishment of tumors favor this experimental brain-tumor model. This should be an excellent model for study of experimental therapies.

Invasive phenotype observed in 1,3-bis(2-chloroethyl)-1-nitrosourea—resistant sublines of 9L rat glioma cells: a tumor model mimicking a recurrent malignant glioma

2004 ◽  
Vol 101 (5) ◽  
pp. 826-831 ◽  
Author(s):  
Ryuta Saito ◽  
John Bringas ◽  
Hanna Mirek ◽  
Mitchel S. Berger ◽  
Krys S. Bankiewicz
Keyword(s):  
Drug Resistance ◽  
Tumor Model ◽  
Growth Patterns ◽  
Invasive Growth ◽  
Content Type ◽  
Rat Glioma ◽  
Brain Tumor Model ◽  
Fine Print

Object. Chemotherapy is suspected of having an effect on the generation of phenotypical heterogeneity and the development of drug resistance in tumors. Recurrent gliomas feature drug resistance as well as greater invasive growth than original tumors. The authors investigated phenotypical changes in invasion observed in 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)—resistant sublines of the 9L rat gliosarcoma. Methods. Two established BCNU-resistant sublines, derived from 9L gliosarcoma cells by treating these cells with BCNU in vivo or in vitro, were used in the study. An in vitro examination confirmed the resistance of the cells to BCNU treatment. The cells were implanted into the striatum of Fisher 344 rats, and histological examinations were performed to compare the growth patterns of the resultant tumors. A new brain tumor model was established by implanting 9L-2 cells in Fisher 344 rats. The 9L-2 and BTRC-19 cells displayed a distinct increase in BCNU resistance compared with the 9L cells. Both BCNU-resistant sublines developed a tumor mass with invasive margins, which is not the case with 9L tumor models. The newly developed 9L-2 tumor model demonstrated 100% tumor uptake with consistent growth patterns. Conclusions. Cells that acquire drug resistance also demonstrated invasive growth. Because the 9L-2 and BTRC-19 cells were derived from 9L cells that had been treated with BCNU in vivo and in vitro, this change in phenotype was likely caused by the drug treatment, which may have implications for chemotherapy of gliomas. The tumor model that developed from the 9L-2 cells can be used as a model of a recurrent glioma, which features drug resistance and invasive growth.

Combined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model

1981 ◽  
Vol 54 (4) ◽  
pp. 461-467 ◽  
Author(s):  
Alexander M. Spence ◽  
Joseph P. Geraci
Keyword(s):  
Gamma Irradiation ◽  
Survival Time ◽  
Fast Neutron ◽  
Combined Therapy ◽  
Tumor Model ◽  
Survival Times ◽  
Gamma Photon ◽  
Maximum Enhancement ◽  
Content Type ◽  
Fine Print

✓ The combination of cyclotron fast-neutron radiotherapy with BCNU chemotherapy was compared to 137Cs gamma photon radiotherapy combined with BCNU in the 36B-10, F-344 rat-transplanted glioma model. Radiation and drug treatments were administered 7 to 8 days after intracerebral tumor implantation. Increase in animal survival time was used as the measure of the effectiveness of various treatment schedules. Single-dose neutron or gamma radiotherapy was tested on Day 7 over the ranges 0 to 900 rads and 0 to 2000 rads, respectively. This therapy produced increases in mean survival times up to 70% at the highest radiation doses. When BCNU (10 mg/kg body weight) was administered intravenously on Day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35% to 50%, irrespective of the dose or type of irradiation. In contrast, by using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 hour before either neutron or gamma irradiation on Day 7, there was enhancement of the radiation effect by BCNU. Under these conditions, the maximum enhancement of the mean survival time was 70% to 75% in neutron-treated animals and 120% to 150% in gamma-treated animals. Treatment with BCNU 1 hour before or 1 day after neutron irradiation proved to be no more effective in improving the survival time of tumor-bearing animals than the drug similarly combined with conventional gamma irradiation.

A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein—13 adenoviral gene therapy

2001 ◽  
Vol 95 (2) ◽  
pp. 298-307 ◽  
Author(s):  
Gregory A. Helm ◽  
Jin Zhong Li ◽  
Tord D. Alden ◽  
Sarah B. Hudson ◽  
Elisa J. Beres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Skeletal Development ◽  
Light And Electron Microscopy ◽  
Mesenchymal Cell ◽  
Ultrastructural Changes ◽  
Endochondral Bone Formation ◽  
Electron Microscopic ◽  
Content Type ◽  
Time Points ◽  
Fine Print

Object. Bone morphogenetic proteins (BMPs) are involved in the growth and development of many tissues, but it is their role in skeletal development and their unique ability to induce ectopic and orthotopic osteogenesis that have attracted the greatest interest. Expression of the BMP-13 gene is predominantly localized to hypertrophic chondrocytes in regions of endochondral bone formation during development, as well as in mature articular cartilage in the adult. In addition, the application of BMP-13 on a collagen carrier induces neotendon/neoligament formation when delivered subcutaneously or intramuscularly in rodents. The aim of the present study was to determine the histological and ultrastructural changes that occur after the intramuscular injection of a first-generation BMP-13 adenoviral vector. Methods. Athymic nude rats were injected with 3.75 × 1010 plaque-forming units of adenovirus (Ad)-BMP-13 or Ad-β-galactosidase in the thigh musculature, and the region was examined using light and electron microscopy at various time points between 2 days and 100 days postinjection. As early as 2 days after injection of Ad-BMP-13, progenitor cells were observed infiltrating between the transduced muscle fibers. These cells subsequently proliferated, differentiated, and secreted large amounts of collagenous extracellular matrix. By 100 days postinjection, the treated tissue displayed the histological and ultrastructural appearance of neotendon/neoligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the treated tissue. A short-term bromodeoxyuridine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection. At all time points, the control AD-β-gal injection sites were found to contain only normal muscle, without evidence of inflammation or mesenchymal cell proliferation. Conclusions. The results of this study indicate that in the future the use of the BMP-13 gene may have therapeutic utility for the healing of tendon and ligament tears and avulsion injuries.

Tumor-associated neurological dysfunction prevented by lazaroids in rats

1991 ◽  
Vol 74 (1) ◽  
pp. 112-115 ◽  
Author(s):  
Wesley A. King ◽  
Keith L. Black ◽  
Kiyonobu Ikezaki ◽  
Scott Conklin ◽  
Donald P. Becker
Keyword(s):  
Vascular Permeability ◽  
Tumor Model ◽  
Neurological Dysfunction ◽  
Control Group ◽  
Content Type ◽  
Brain Tumor Model ◽  
Walker 256 ◽  
Walker 256 Tumors ◽  
Fine Print ◽  
Better Than

✓ 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.

Focal brain edema associated with acute arterial hypertension

1986 ◽  
Vol 64 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Shizuo Hatashita ◽  
Julian T. Hoff ◽  
Shozo Ishii
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Water Content ◽  
Brain Edema ◽  
Evans Blue ◽  
Blue Dye ◽  
Boundary Zone ◽  
Tissue Pressure ◽  
Content Type ◽  
Fine Print

✓ Acute arterial hypertension was studied in normal cats to determine its role in the formation of brain edema. Arterial hypertension was induced for 30 minutes by inflation of a balloon catheter situated in the descending aorta. Cerebral edema was evaluated by gross and microscopic observations, tissue water content by wet/dry weights, and blood-brain barrier (BBB) permeability by extravasation of horseradish peroxidase (HRP) and Evans blue dye. For 1 hour after the hypertensive insult, tissue pressure and regional cerebral blood flow (rCBF) were measured from the arterial boundary zone and from a non-boundary region, and intracranial pressure was recorded from the lateral ventricle as ventricular fluid pressure. Focal lesions with increased BBB permeability to Evans blue dye or HRP were usually located symmetrically in the cortex, corresponding to the occipitoparietal parts of the arterial boundary zones. The increase in water content was found only in areas of increased permeability. Tissue pressure increased simultaneously with the abrupt rise in blood pressure, and an increase in rCBF paralleled the elevation of blood pressure. Tissue pressure and rCBF returned to a steady state when blood pressure returned to normal. There were no differences in tissue pressure or rCBF between the arterial boundary zone and the non-boundary zone, even during arterial hypertension. In cerebral hemispheres examined 48 hours after the hypertensive challenge, brain edema had not continued to develop. The data indicate that acute arterial hypertension may produce focal brain edema with increased permeability of the BBB in the cortex of normal brain, particularly in the arterial boundary zones. The authors postulate that increased cerebral blood volume, high intraluminal pressure, and breakthrough of autoregulation play an important role in the formation of hypertensive brain edema.

Subtotal neonatal calvariectomy

1979 ◽  
Vol 51 (5) ◽  
pp. 691-696 ◽  
Author(s):  
Laurence W. Mabbutt ◽  
Vincent G. Kokich ◽  
Benjamin C. Moffett ◽  
John D. Loeser
Keyword(s):  
Postoperative Period ◽  
Surgical Margin ◽  
Regenerative Process ◽  
Bone Union ◽  
Histological Techniques ◽  
Content Type ◽  
Rate Of Development ◽  
Definite Pattern ◽  
Fine Print

✓ A subtotal calvariectomy was performed on rabbits between 10 and 14 days of age. The animals were allowed to grow and were then sacrificed serially so that the sutural and skeletal redevelopment could be analyzed through a combination of gross, radiographic, and histological techniques. The results indicate that calvarial regeneration is a progressive process with a definite pattern and rate of development. During the regenerative process, bone was deposited both at the surgical margin and as islands within the surgical defect. The eventual approximation of these areas of ossification produced multiple fibrous articulations. The majority of these articulations were obliterated by bone union, except for the midsagittal, coronal, and metopic sutures, which were re-established in their appropriate anatomical positions. The maintenance of dural integrity during the surgical phase and the regeneration and establishment of pericranial continuity during the postoperative period were believed to be important in the re-establishment of normal sutural and skeletal architecture.

Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study

2000 ◽  
Vol 93 (4) ◽  
pp. 634-639 ◽  
Author(s):  
Behnam Badie ◽  
Jill M. Schartner ◽  
Jasmeet Paul ◽  
Becky A. Bartley ◽  
Jessica Vorpahl ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Brain Tumors ◽  
Ex Vivo ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Content Type ◽  
Rat Glioma ◽  
Infiltrating Cells ◽  
Glioma Model ◽  
Fine Print

Object. Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model.Methods. Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c—highly positive, CD45—slightly positive cell), macrophage (CD11b/c—highly positive, CD45—highly positive cell), lymphocyte (CD11b/c-negative, CD45—highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry.Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 ± 3% and 33 ± 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 ± 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42).Conclusions. Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.

Reconstruction of the MCA bifurcation after excision of a giant aneurysm

1988 ◽  
Vol 68 (6) ◽  
pp. 974-977 ◽  
Author(s):  
W. Michel Bojanowski ◽  
Robert F. Spetzler ◽  
L. Philip Carter
Keyword(s):  
Doppler Ultrasonography ◽  
Operative Procedure ◽  
Giant Aneurysm ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
History Of ◽  
Microsurgical Techniques ◽  
Left Middle ◽  
Good Flow ◽  
Fine Print

✓ A patient with a giant aneurysm of the left middle cerebral artery (MCA) presented with a history of subarachnoid hemorrhage and ischemic symptoms. When the aneurysm was explored, its base was found to be very firm and atherosclerotic. Temporary clips were applied to the MCA, the aneurysm was excised, and the MCA bifurcation was reconstructed using microsurgical techniques. Good flow in the reconstructed MCA trunk was demonstrated by intracranial Doppler ultrasonography. A description of the operative procedure is presented.

Natural history of postoperative aneurysm rests

1987 ◽  
Vol 66 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Isaac Feuerberg ◽  
Christer Lindquist ◽  
Melker Lindqvist ◽  
Ladislau Steiner
Keyword(s):  
Natural History ◽  
Content Type ◽  
Follow Up Studies ◽  
History Of ◽  
Microsurgical Techniques ◽  
Fine Print ◽  
Saccular Aneurysms

✓ In a series of 715 patients operated on by microsurgical techniques for intracranial saccular aneurysms between 1970 and 1980, part of the aneurysmal sac was not obliterated in 28 aneurysms in 27 patients (3.8% of 715 cases). Clinical follow-up evaluation for 8 years (range 4 to 13 years) and angiographic follow-up studies for 6 years (range 2 to 10 years) in these 27 cases revealed that one aneurysm rest increased in size and bled twice, five were spontaneously obliterated, two decreased in size, 13 remained unchanged, and in seven cases no late follow-up angiography was performed. The incidence of rebleeding from an aneurysm rest was 3.7% of the 27 in whom the sac was not obliterated and 0.14% of all 715 patients who were operated on.

Improved treatment of a brain-tumor model

1983 ◽  
Vol 58 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Mark L. Rosenblum ◽  
Massimo A. Gerosa ◽  
Dolores V. Dougherty ◽  
Charles B. Wilson
Keyword(s):  
Brain Tumor ◽  
Tumor Model ◽  
Clinical Effects ◽  
Content Type ◽  
Animal Survival ◽  
Fractionation Schedule ◽  
Brain Tumor Model ◽  
Clonogenic Cell ◽  
Survival Studies ◽  
Fine Print

✓ Clonogenic cell and animal survival studies were used to determine the most effective BCNU therapy schedule in the 9L rat brain-tumor model. Survival of tumor cells following a single LD10 dose of BCNU (13.3 mg/kg intraperitoneally) was compared to cell survival after one to four daily 0.5 × LD10 doses. The posttreatment kinetics of surviving clonogenic cells were investigated at various times after BCNU was given in single doses of 0.25 to 1 × LD10 and in two daily doses of 0.5 × LD10. The cell kill was greater, time to reinitiation of cell growth was later, posttreatment rate of clonogenic cell proliferation was slower, and the interval to total repopulation of the clonogenic cell pool was longer with a single LD10 dose as compared to the multiple-dose schedules. Animal survival studies confirmed that a single LD10 dose of BCNU was at least as effective as a cumulative level of up to 1½ times that amount when treatment was administered in smaller doses, regardless of the fractionation schedule. Clinical experience with patients harboring malignant brain tumors has shown that a single BCNU dose of 185 to 200 mg/sq m is tolerated well. Results of these animal experiments suggest that this therapy should have anti-tumor activity at least equivalent to the more commonly employed schedule of 80 mg/sq m/day given for 3 days. Although direct comparison of treatment efficacy using the two schedules is not possible, no adverse clinical effects have been observed with the recently adopted single-dose schedule. Furthermore, the duration of patient hospitalization for chemotherapy has decreased.

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