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Oxygenation of the rat 9L gliosarcoma and the rat 13672 mammary carcinoma with various doses of a hemoglobin solution.

Tumor oxygen tensions were measured using a computer controlled pO2 microelectrode in two preclinical solid tumor models, the rat 9L gliosarcoma and the rat 13672 mammary carcinoma. Tumor oxygenation profiles were determined under four conditions: 1) normal air breathing, 2) carbogen (95% O2/5% CO2) breathing, 3) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with normal air breathing and 4) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with carbogen breathing. Both tumors had severely hypoxic regions under normal air breathing conditions. Although carbogen breathing increased the oxygenation of the better oxygenated portions of the tumor, it did not impact on the severely hypoxic tumor regions. Administration of the hemoglobin solution was effective in increasing the oxygenation throughout both tumors under normal air breathing conditions. The addition of carbogen breathing to administration of the hemoglobin solution eliminated severe hypoxia in the 9L gliosarcoma and markedly reduced the severely hypoxic regions of the 13672 mammary carcinoma.

Animals↗

Radiation-induced gliosarcoma. Case report and review of the literature.

A 13-year-old boy presented with a cerebral gliosarcoma 12 years after having acute lymphoblastic leukemia treated by chemotherapy and central nervous system prophylaxis treated by radiation therapy (24 Gy) and intrathecal methotrexate. A review of the literature disclosed 129 possible radiation-induced gliomatous and/or sarcomatous brain tumors: namely, 89 gliomas, 36 sarcomas, and four gliosarcomas, including the present case. An analysis of these cases revealed several characteristics that differentiate them from similar spontaneous brain tumors, thus providing arguments for the carcinogenic effect of radiation therapy on intracranial tumors.

Brain Neoplasms↗

Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats.

OBJECT: Interleukin-12 (IL- 12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered IL-12 in a malignant brain tumor model. METHODS: After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9L gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription-polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells. The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma. CONCLUSIONS: These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.

Animals↗

Primary C1-2, intradural, extramedullary meningeal sarcoma with glial fibrillary acidic protein-immunoreactive components: a spinal gliosarcoma? Case report and review of the literature.

The authors report an exceedingly rare case of a patient harboring a primary, spinal, C1-2, intradural, extramedullary meningeal sarcoma in which there were glial fibrillary acidic protein-immunoreactive components, but, importantly, no physical connection with neural tissue. On initial diagnostic imaging, neuroradiological features suggestive of a spinal meningioma were demonstrated in this 73-year-old man. He underwent a C1-2 laminectomy and removal of the posterior ring of the foramen magnum, and the lesion was excised. Histological and immunohistochemical testing showed a gliosarcoma. The clinical, radiological, and operative data are reviewed, as are the histopathological findings. To the authors' knowledge, this is the first case of a primary spinal intradural extramedullary gliosarcoma reported in the literature.

Aged↗

Gliosarcoma with areas of primitive neuroepithelial differentiation and extracranial metastasis.

We report a case of gliosarcoma with areas of primitive neuroepithelial differentiation arising in the temporal lobe of a 53-year-old man. The sarcomatous component of this tumor was perivascular in its distribution and showed expression of factor VIII-related antigen, smooth muscle actin and CD34. The primitive neuroepithelial component possessed a small cell morphology and showed expression of neuronal antigens. Strong expression of p53 was demonstrated throughout the tumor with only focal weak expression of epidermal growth factor receptor. The tumor developed widespread extraneural metastases 5 months after surgical resection of the primary tumor. Histological examination of the liver metastases showed them to consist predominantly of the primitive neuroepithelial component. We believe this to be a novel pattern of differentiation in a gliosarcoma which in this case was associated with an aggressive metastatic potential.

Biomarkers, Tumor↗

A lateral ventricular gliosarcoma arising in an ependymoma.

OBJECTIVE: We describe a 29-year-old man with gliosarcoma in the lateral ventricle. CASE: The patient presented with headache and impairment of consciousness. Computed tomography and magnetic resonance imaging localized the tumor to the right lateral ventricle and showed heterogeneous enhancement with administration of contrast agents. The tumor was partially removed via a transcallosal approach. Histologic examination disclosed gliosarcoma arising by malignant transformation of an ependymoma. POST-OPERATIVE COURSE: The patient died of tumor progression 78 days after admission, despite intensive radiotherapy and chemotherapy.

Adult↗

Spinal gliosarcoma: a light, immunohistochemical and ultrastructural study.

Gliosarcomas are mixed tumors of the brain containing both malignant neuroectodermal and mesenchymal components. Over 100 cases have been reported within the brain; however, to our knowledge, this is the first reported case located primarily within the spinal cord. Along with a review of the literature, the light, immunohistochemical and ultrastructural findings of a spinal gliosarcoma are reported in a 41-year-old woman with a previously diagnosed oligodendroglioma of the cerebellum 15 years earlier and a concurrent pituitary adenoma. The spinal tumor appears to be morphologically identical to its intracranial counterpart.

Adult↗

Radiation-associated gliosarcoma.

The authors report a case of radiation-associated intracerebral gliosarcoma with fibrosarcomatous predominance, arising at the site of a low-grade glioma treated 10 years previously. The features of this case conform to the accepted criteria for radiation-induced tumour, in that the tumour developed within the radiation field, differed dramatically in histologic features from the original tumour and did not develop until 10 years after treatment. Although such tumours are most uncommon, this case suggests that radiation-induced gliosarcoma should be considered in the differential diagnosis of recurrent mass at the site of a treated intracranial neoplasm.

Adolescent↗

NKR-P1+ cells localize selectively in Rat 9L gliosarcomas but have reduced cytolytic function.

To better understand immune responses to brain tumors and to develop possible approaches for immunotherapy, we have investigated the leukocyte populations infiltrating the rat 9L gliosarcoma. By immunocytochem-ical analyses of the cells infiltrating the tumor, we observed a substantial number of cells expressing natural killer cell receptor protein 1 (NKR-P1), a marker expressed only on rat lymphocytes capable of non-MHC-restricted cytotoxicity. Previous investigations have determined the existence of three populations of NKR-P1+ lymphocytes in normal rats, including NKR-P1bright/T-cell receptor (TCR)-/CD3-/CD5- (approximately 5-15%), NKR-P1dim-/TCRalphabeta+/CD3+/CD5+ (approximately 1-5%), and NKR-P1dim/TCRgammadelta+/CD3+/CD5+ (approximately 0.5-2%). By one-parameter flow cytometry, it was determined that NKR-P1+ cells constituted 30-60% of the lymphocytes in 9L tumors. Among splenic lymphocytes or peripheral blood leukocytes, NKR-P1bright cells are 1.5-4.5 times more numerous than NKR-P1dim cells. In striking contrast, NKR-p1dim cells were 4-5 times more numerous than NKR-P1bright cells among lymphocytes isolated from 9L tumors. Using quantitative analyses of laser confocal microscopic scans, we determined that NKR-P1dim cells were approximately 4 times as numerous as NKR-P1bright cells in situ, confirming flow cytometric findings. By two-color now cytometric analyses, it was observed that approximately 5-10% of the cells were NKR-p1bright/CD5-/TCR-, a phenotype representative of NK cells. Also, approximately 11-25% of the cells were NKR-P1dim/CD5+/TCR+ cells, corresponding to the T-cell subset with non-MHC-restricted lytic function. In addition, we observed a cell population among 9L-derived lymphocytes with a NKR- p1dim/CD5-/TCR- phenotype (approximately 15-25%). Cells of this phenotype have not been reported previously, and most likely represent NK cells down-modulated for expression of NKR-P1. Alternatively, they might represent cells of unknown origin or cells down-modulated for expression of T-cell markers in the microenvironment of 9L tumors. We also compared the lytic capacity of NKR-P1+ populations derived from normal animals and from 9L gliosarcomas. In these experiments, it was determined that, although cells isolated from 9L tumors had some capacity to lyse tumor target cells, they were clearly less efficient than cells isolated from normal splenocytes. Cumulatively, these data suggest that there is selective localization of cells capable of mediating antitumor responses in 9L, but that tumor-associated factors may down-regulate their function and expression of NKR-P1.

Animals↗

[Histopathological and immunohistochemical studies on gliosarcoma].

Immunohistochemical staining of 5 gliosarcomas was performed. Neoplastic glial component stained positive by GFAP. Endothelial cells lining the lumina of glomeruloid vascular structures stained positively with both UEA-1 and FVIII/RAg antibodies. Mesenchymal cells of sarcomatous areas stained positively with SMSA antibody and presence of PDGFR. The staining results demonstrate that the sarcomatous component of gliosarcoma is of smooth muscle origin and suggest that the vascular smooth muscle hyperplasia is related to PDGF.

Aged↗

[Gliosarcomas].

Gliosarcomas are rare tumors of the central nervous system with a poor prognosis. Histologically these tumors are characterized by an admixture of neoplastic glial cells and sarcomatous elements. Due to the scarcity of data in literature, the diagnosis is often missed and treatment is difficult. The authors report three cases of cerebral gliosarcomas and review the literature on this subject.

Adult↗

Thorotrast-associated gliosarcoma. Including comments on thorotrast use and review of sequelae with particular reference to lesions of the central nervous system.

The occurrence of a glioblastoma with sarcoma, a gliosarcoma, in the left frontal-temporal area of a 49-year-old woman with a history of Thorotrast exposure, is described. Thorotrast-laden histiocytes and free Thorotrast material were found in both components of the tumor. An overlying, adherent dural cranial lesion was found to contain massive deposits of Thorotrast embedded in a dense fibrotic and sclerotic stroma with focal calcification. These features are typical of "Thorotrastoma." Thorotrast stains greenish-brown with hematoxylin and eosin and appears as refractile granular particles of relatively uniform size either within histiocytes or as free material. The radioactivity of the deposits was confirmed through the use of a scintillation counter, and 232 thorium was definitively identified though the use of scanning electron microscopy with energy-dispersive X-ray analysis. Immunohistochemical studies of the tumor demonstrated glial fibrillary acid protein (GFAP) immunoreactivity in areas of glioma and focal vimentin and actin immunoreactivity in areas of sarcoma. Thorotrast-associated lesions of the central nervous system (CNS) are infrequently reported, and a Thorotrast-associated gliosarcoma has not yet been reported. The use of Thorotrast, its radiobiology, and sequelae are reviewed with particular emphasis on lesions occurring in the CNS.

Brain Neoplasms↗

Gliosarcoma with cartilage formation.

A case of gliosarcoma with cartilaginous component is described. Immunohistochemical and electron microscopic studies confirmed the presence of glial and fibroblastic elements. A major part of the sarcomatous tissue was undifferentiated and not labeled by any of the markers used including those for endothelial cells. The cartilage cells also were not labeled either by antiglial fibrillary acidic protein or any other marker. The occurrence and histogenesis of cartilage in gliomas and gliosarcomas have been reviewed.

Brain Neoplasms↗

Distribution of p53 protein expression in gliosarcomas: an immunohistochemical study.

The wild-type p53 gene product is a nuclear phosphoprotein that suppresses cell and tumor growth. Mutations of the p53 gene are by now the most frequently recognized genetic alterations in human malignancies and occur in many types of carcinomas as well as in astrocytomas and sarcomas. Wild-type p53 protein has a short half-life, is present in very low quantities in normal cells and cannot be detected immunohistochemically. Mutant p53 proteins have longer half-lives and are usually present in immunohistologically detectable amounts. It is generally agreed that the presence of p53 immunostaining indicates the presence of an abnormal p53 protein and is strongly suggestive of a mutation in the p53 gene. In this study, we stained paraffin sections from eight samples of gliosarcomas from seven patients with an antibody to p53. All tumors contained p53-immunoreactive nuclei in both the glial and the sarcomatous component. In five tumors, a majority of nuclei was positive in the sarcomatous component while only a minority of nuclei was positive in the glial areas. In one tumor, the reverse was seen. In another tumor, approximately half the nuclei were positive in both components and in one tumor, only a minority of nuclei were positive in either component (this lesion was the recurrence of a tumor in which the majority of the sarcoma's nuclei had been positive). These data indicate that p53 mutations may play a role in the pathogenesis of gliosarcomas and suggest an origin of both the glial and sarcomatous components from a common progenitor.

Adult↗

Histogenesis of sarcomatous component of the gliosarcoma: an ultrastructural study.

This report describes the ultrastructural findings of the sarcomatous component in five cases of gliosarcoma. The tumor contained a heterogenous population of cells with collagen scattered in the interstitium. Three main cell types were found: histiocyte-like cells, fibroblast-like cells and undifferentiated cells. The histiocyte-like cells had oval nuclei, short and flat rough endoplasmic reticulum, prominent Golgi apparatus, lysosomes, phagocytic vacuoles, ruffled cytoplasmic membrane with filopodia, segmental basal lamina and occasional intercellular junctions. The fibroblast-like cells had elongated nuclei, prominent cisterns of rough endoplasmic reticulum and microfilaments. The undifferentiated cell cytoplasmic processes suggesting differentiation toward histiocyte-like cell. In addition, intermediate cells, myofibroblasts, multinucleated giant cells and xanthomatous cells were also present. Occasional glial processes were interposed between tumor cells. Some were enclosed by cytoplasmic processes of histiocyte-like cells and others engulfed within the cytoplasm. Capillary showed surface infoldings, fenestrations of endothelial cells, thickened basal lamina, occasional pericytes and scattered collagen. Some capillaries were surrounded by aggregating histiocyte-like cells and undifferentiated cells. The present findings suggest that (a) the sarcomatous component in gliosarcoma is likely derived from undifferentiated cells with a broad differentiation into histiocytic, fibroblastic and other cell types, (b) endothelial cells and pericytes may not participate in sarcomatous development, (c) capillaries within the sarcomatous component are of non-gliomatous type, and (d) the histiocyte-like cells are capable of phagocytizing glial elements.

Adult↗

The effects of irradiation on major histocompatibility complex expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model.

The effects of irradiation on major histocompatibility complex (MHC) expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model were examined. Doses of irradiation administered were biologically equivalent to that used in the treatment of patients with malignant gliomas. No significant change in immune parameters was observed following irradiation in the normal rat brain. In the 9L gliosarcoma model irradiation did not suppress MHC expression or lymphocytic infiltration. These findings suggest that prior exposure to therapeutic irradiation need not adversely affect subsequent immunotherapies, and provide a foundation for future studies of immunomodulation in the irradiated brain.

Animals↗

Sarcoma arising from a gliosarcoma.

An 18-year-old woman with headaches and visual abnormalities was found upon biopsy to have an occipital gliosarcoma, which was treated with irradiation and chemotherapy for a year. Cells in the gliosarcoma tissue were positive for GFAP. At necropsy, only the sarcoma was evident at the site of original surgical removal. The sarcoma had spread widely along meningeal routes, causing the patient's death. The biologic behavior and histologic features of the sarcoma were clearly malignant. Cells cultured from the biopsy specimen maintained features in common with sarcoma.

Adolescent↗

Clinical and pathological study of 24 cases of gliosarcoma.

The authors review the clinical and pathological features of 24 patients with gliosarcoma. The study revealed the following findings. Gliosarcoma occurs more frequently than is indicated in the literature, and in our series was present in 8% of all cases of glioblastoma multiforme. The presenting features are not significantly different from those of glioblastoma multiforme. The lesion often presents itself at surgery as a firm, well circumscribed mass within the temporal lobe, and at surgery it is commonly mistaken for a meningioma. There is an increased likelihood of metastasis compared to that of glioblastoma. The prognosis is no worse than that of glioblastoma, in spite of the addition of sarcomatous elements.

Adult↗