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1.
It is important to evaluate the therapeutic and side effects of new therapy for malignant brain tumors in an adequate animal model prior to its initial clinical investigation. For decades, neurooncologists have argued for the use of primary, autochthonous tumors rather than transplanted tumors such as C 6 glioma cells and 9 L gliosarcoma cells. But unfortunately, no spontaneous animal astrocytomas are currently available as usable models. So we tried to establish the model of primary, autochthonous avian sarcoma virus-induced rat gliomas for experimental chemotherapy and immunotherapy. The present study was undertaken to determine the incidence and histologic pattern of tumors and the mean survival time of the animal model used. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of infectious cell free homogeneous subgroup D Schmidt-Ruppin avian sarcoma virus (SR-D-ASV) into 3-day-old inbred Fischer 344 rats induced small sized tumors in all rats 20 days later. The mean survival time of inoculated rats were 58.7 +/- 12 days. As to the classification of SR-D-ASV induced brain tumors in Fischer rats, astrocytoma was 70.6% (protoplasmic astrocytoma 23.5%, fibrillary astrocytoma 47.1%), sarcoma 17.6%, and mixed astrocytoma and sarcoma 11.8%. In conclusion, this SR-D-ASV induced tumor in the rat fulfilled the following criteria for the desirable animal model: (1) Spontaneously arising. (2) Glial origin. (3) Intraparenchymal growth. (4) Uniformly fatal within reasonable time period. Statistic evaluation of the effects of chemotherapy and immunotherapy was considered to be possible.  相似文献   

2.
Lewis rats bearing avian sarcoma virus (ASV)-induced brain tumors were injected with guinea pig spinal cord emulsion and complete Freund's Adjuvant to determine if they remained susceptible to induction of experimental allergic encephalomyelitis (EAE). The incidence of EAE among rats with small, and moderate sized gliomas was similar to non-tumor-bearing controls (P<0.5; P<0.9) while 18 o24 (75%) animals with large gliomas developed EAE as compared to 31 of 33 (93%) controls (P<0.05). The histologic features and geographical distribution of ‘ordinary’ EAE were seen in controls and were maintained in tumor-bearing rats. The presence of an intracranial tumor did not significantly alter the ability of Lewis rats to develop EAE.  相似文献   

3.
The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology of tumors induced by a uniform inoculum of the Bratislava-77 strain of ASV in adult, neonatal, and fetal Fischer 344 rats. Post-inoculation mortality varied significantly between groups inoculated at 1, 10 and 100 days and was most precipitous in perinatally inoculated rats. Percentage of tumor induction declined from 100% among rats inoculated at 1 day of age to 50% among rats inoculated at 100 days of age. The mean number of tumors/animal was inversely proportional to the logarithm of the age at inoculation. A large majority of tumors in each group were glial; the remainder were mesenchymal and mixed glial and mesenchymal. Neuroglial tumors included: mixed gliomas with oligodendroglial and astrocytic elements; and gemistocytic, pilocytic, fibrillary, anaplastic and protoplasmic astrocytomas. Tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in older animals tended to be purely astrocytic and of uniform cell type. Mesenchymal tumors occurred primarily in the meninges and were common among animals inoculated perinatally but were rare among animals inoculated as adults. No neuronal tumors were encountered even among rats inoculated as early as 16 days of gestation.  相似文献   

4.
A Watanabe 《Brain and nerve》1988,40(7):637-645
The correlations between blood flow or glucose metabolism and distribution of DNA synthesizing cells were simultaneously investigated in the same rat brain tumors using autoradiographic technique and immunoperoxidase stain. Two rat brain tumor strains (A and B) induced by Rous sarcoma virus were used. A suspension of 1 X 10(4) rat brain tumor cells was stereotactically implanted into the right basal ganglia of syngenic Fischer 344/Du Crj rats. The tumor strain A bearing rats died 12.0 +/- 1.8 days and the tumor strain B bearing rats died 17.6 +/- 1.3 days after the tumor implantation. Blood flow and glucose metabolism were measured with 14C-iodoantipyrine and 14C-2-deoxy-D-glucose autoradiography. All rats also received a 1-h i.v. infusion of BrdU, 5-20 mg, at the autoradiographic procedure. The immunoperoxidase staining for BrdU (Avidin Biotin peroxidase complex method) and other conventional stainings were performed in the sections alternating with the autoradiographic sections. BrdU-positive nuclei (S-phase cells) were heterogeneously distributed and labeling index ranged from less than 1% to more than 40% in the tumors. Neoplastic vessels tended to be distributed in the peripheral part of the tumor and were surrounded with S-phase cells in a part of the tumor. The blood flow was heterogeneously distributed in the tumor and the average blood flow reduced to about 50% in the tumor strain A and to about 60% in the tumor strain B, respectively in comparison with contralateral cortex. The distribution of blood flow did not correlate with the distribution of S-phase cells nor the distribution of neoplastic vessels.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
Integrins are expressed in tumor cells and tumor endothelial cells, and likely play important roles in glioma angiogenesis and invasion. We investigated the anti‐glioma mechanisms of cilengitide (EMD121974), an αvβ3 integrin inhibitor, utilizing the novel invasive glioma models, J3T‐1 and J3T‐2. Immunohistochemical staining of cells in culture and brain tumors in rats revealed positive αvβ3 integrin expression in J3T‐2 cells and tumor endothelial cells, but not in J3T‐1 cells. Established J3T‐1 and J3T‐2 orthotopic gliomas in athymic rats were treated with cilengitide or solvent. J3T‐1 gliomas showed perivascular tumor cluster formation and angiogenesis, while J3T‐2 gliomas showed diffuse single‐cell infiltration without obvious angiogenesis. Cilengitide treatment resulted in a significantly decreased diameter of the J3T‐1 tumor vessel clusters and its core vessels when compared with controls, while an anti‐invasive effect was shown in the J3T‐2 glioma with a significant reduction of diffuse cell infiltration around the tumor center. The survival of cilengitide‐treated mice harboring J3T‐1 tumors was significantly longer than that of control animals (median survival: 57.5 days and 31.8 days, respectively, P < 0.005), while cilengitide had no effect on the survival of mice with J3T‐2 tumors (median survival: 48.9 days and 48.5, P = 0.69). Our results indicate that cilengitide exerts a phenotypic anti‐tumor effect by inhibiting angiogenesis and glioma cell invasion. These two mechanisms are clearly shown by the experimental treatment of two different animal invasive glioma models.  相似文献   

6.
9L/Fischer344与C6/Wistar两种大鼠脑胶质瘤模型的比较研究   总被引:2,自引:2,他引:0  
目的探讨9L/Fischer344和C6/Wistar两种大鼠脑胶质瘤模型的对比研究。方法采用立体定向技术,大鼠脑内接种定量的肿瘤细胞建立模型,比较两种模型大鼠脑内肿瘤生长情况;采用免疫组织化学方法,比较两种模型脑内肿瘤局部细胞免疫反应情况。结果(1)9L/Fischer344大鼠脑内有肿瘤持续生长,而C6/Wistar大鼠脑内早期可见肿瘤生长,但肿瘤局部有大量淋巴细胞浸润,肿瘤周边血管呈现“淋巴细胞血管套”现象,后期脑内肿瘤逐渐消退、消失,仅见残留轨迹和含褐色素沉着的吞噬细胞;(2)9L/Fischer344肿瘤局部可见CD68阳性细胞,未见CD4、CD8阳性细胞,而C6/Wistar肿瘤局部CD68阳性细胞数量明显较9L模型多(P<0.01),并可见CD4、CD8阳性的淋巴细胞。结论9L/Fischer344模型稳定性高,重复性好,肿瘤局部T淋巴细胞浸润极少,是一种较为理想的脑胶质瘤免疫治疗研究的动物模型;C6/Wistar模型脑内肿瘤不能持续生长,脑内肿瘤可自发性消退,肿瘤局部T淋巴细胞浸润明显,存在较强的细胞免疫反应,可能是肿瘤的消退的原因,该模型不适合用于胶质瘤治疗,尤其是免疫治疗的实验研究。  相似文献   

7.
Lewis rats are more likely to self-administer various drugs of abuse than Fischer rats. Here these two strains of rats were compared with regard to basal brain opioid peptide levels and the response to chronic morphine treatment and to naloxone-precipitated withdrawal. Lewis rats had lower basal dynorphin peptides in the substantia nogra, striatum (not Leu-enkephalinArg6) and VTA (not dynorphin B) and the pituitary gland. Leu-enkephalinArg6 levels were also lower in these structures (with the exception of striatum which had higher levels) and in the nucleus accumbens. There were also strain differences in the response to chronic morphine treatment; in the nucleus accumbens, morphine treatment increased dynorphin A levels in Fischer rats only, in the ventral tegmental area effects were opposite with increased dynorphin levels in Fischer and decreased levels in Lewis rats, in the hippocampus dynorphin levels were markedly reduced in Lewis rats only. In Fischer rats, chronic morphine strongly affected peptide levels in the substantia nigra and striatum, whereas Lewis rats responded less in these areas. Leu-enkephalin, which derives from both prodynorphin and proenkephalin, and Met-enkephalin, which derives from proenkephalin, were effected by chronic morphine mainly in Fischer rats, increasing levels in most of the brain areas examined. The results in this study show (1) strain differences in basal levels of prodynorphin-derived opioid peptides, (2) the prodynorphin system to be differently influenced by morphine in Lewis rats than in Fischer rats and 3) the proenkephalin system to be influenced by chronic morphine in brain areas related to reward processes only in Fischer rats.  相似文献   

8.
We evaluated the efficacy of adenoviral-mediated gene therapy of experimental spinal cord tumors and the functional outcome after this treatment. Spinal cord tumors were generated in the thoracic region of the spinal cord in Fischer 344 rats by stereotaxic intramedullary injection of 1 × 104 9L gliosarcoma cells. Seven days after tumor cell injection, a replication-defective adenoviral vector carrying the herpes simplex virus thymidine kinase gene (ADV-tk) or a control adenoviral vector carrying the β-galactosidase gene (ADV-βgal) was injected into the tumors. Beginning 12 h later the animals were treated with the antiviral drug ganciclovir (GCV; 50 mg/kg) or saline twice a day for 6 days. The neurological performance of the animals was assessed during and following treatment. Eighteen days after tumor cell injection, all of the control animals had paraplegia and large tumors. In contrast, no tumors were detected in animals treated with ADV-tk and GCV. In long-term studies, two of the 5 animals treated with ADV-tk and GCV remained tumor-free and remained neurologically intact at 6 months whereas all animals in the control groups became paraplegic within 18 days.  相似文献   

9.
Intracarotid low dose bradykinin infusion can selectively increase permeability in brain tumor capillaries. However, the mechanism by which bradykinin selectively increases transport into brain tumors and not normal brain has not been clearly defined. This study therefore sought to determine whether the mechanism by which bradykinin increases tumor permeability specifically involves the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27 Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [14C] sucrose was determined using quantitative autoradiography. Bradykinin (10 μg kg1 min1) increased the transport of sucrose to tumors 2.1-fold compared to saline infusion alone (p<0.001). The uptake of sucrose in tumors was significantly inhibited by the bradykinin B2 receptor antagonist,

-Arg, [Hyp3, Thi5,8,

-Phe7]-bradykinin (p<0.01), but not by the B1 receptor antagonist, des-Arg9, [Leu8]-bradykinin. The distribution of B2 receptors in normal brain and tumor tissue was examined by immunohistochemistry using the B2 receptor antiserum, AS 424. High levels of B2 receptors were detected in intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal brain tissue. These results indicate that the permeabilizing effects of bradykinin are mediated through bradykinin B2 receptors, and that differences in distribution of B2 receptors between tumor tissue and normal brain may be responsible for the selective effects on tumor tissue.  相似文献   

10.
The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9LLUC glioma cells syngenic to Fischer 344 (F344) rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9LLUC/F344 rats, and tumor regression was found in some 9LLUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9LLUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9LLUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.  相似文献   

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