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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytic tumors are divided into two basic categories: circumscribed (grade I) or diffuse (grades II-IV). All diffuse astrocytomas tend to progress to grade IV astrocytoma, which is synonymous with glioblastoma multiforme (GBM). GBMs are characterized by marked neovascularity, increased mitosis, greater degree of cellularity and nuclear pleomorphism, and microscopic evidence of necrosis. Several genetic abnormalities have been associated with the development of GBM: In some cases, the abnormality is inherited (e.g., Li-Fraumeni syndrome); in others, genetic alteration appears to result from mutation into an oncogene or deterioration of the tumor-suppressor gene p53. A common, distinctive histopathologic feature of GBM is pseudopalisading. The most common imaging appearance of GBM is a large heterogeneous mass in the supratentorial white matter that exerts considerable mass effect. Less frequently, GBM can occur near the dura mater or in the corpus callosum, posterior fossa, and spinal cord. GBM typically contains central areas of necrosis, has thick irregular walls, and is surrounded by extensive, vasogenic edema, but the tumor may also have thin round walls, scant edema, or a cystic appearance with a mural nodule. GBMs most commonly metastasize from their original location by direct extension along white matter tracts; however, cerebrospinal fluid, subependymal, and hematogenous spread also can occur. Given the rapidly growing body of knowledge about GBM, the radiologist's role is more important than ever in accurate and timely diagnosis.
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PMID:Glioblastoma multiforme: radiologic-pathologic correlation. 894 45

While distant metastases are rare in patients with primary brain malignancies, local growth and invasion are common and life-threatening. Regional infiltration is responsible for the failure of local therapies, resulting in tumor recurrence, progression, and death. The process of invasion requires cellular adhesion, local proteolysis and migration. CAI, carboxyamide-triazole, is an anticancer agent developed as an inhibitor of selected signal transduction pathways. Studies on the effects of CAI on human glioblastoma growth and invasiveness are presented. CAI inhibited proliferation of 6 of 8 cell lines tested in a dose-dependent fashion in vitro (IC50 range 1.5-44 microM), with no effect on the U373 line. Inhibition of adhesion to tissue culture plastic was observed for the H4, T98G, and U373 lines pretreated with CAI; H4 and T98G were inhibited in adhesion to collagen type IV. Incubation with CAI decreased production of the 72 kDa and 92 kDa type IV collagenases in all cell lines, ranging from 16 to 93% inhibition. These observations show that the effects of CAI on cell line behavior can vary between lines that are similar in origin. Despite variability in the inhibitory effects for proliferation and adhesion, CAI is consistently able to inhibit the invasive phenotype of all glioma cell lines in vitro using the Matrigel barrier assay (IC50 range 13-28 microM). These observations suggest that CAI may have benefit in the treatment of gliomas and high grade astrocytomas.
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PMID:Inhibitory effects of CAI in glioblastoma growth and invasion. 912 May 49

Matrix metalloproteinases (MMPs) play an important role in various physiological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to determine the effect of the antitumor compounds cis-dichlorodiammine platinum (ii) (cisplatin) and 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU) on 72-kDa type IV collagenase activity (MMP-2) in human gliomas. Human glioblastoma cell lines were treated with cisplatin (25 microM), and BCNU (50 microM), and the levels of MMP-2 were estimated in serum-free conditioned medium and in cell extracts at different time intervals. Gelatin zymography revealed increased levels of MMP-2 in serum-free conditioned medium and in cell extracts of untreated glioblastoma cell cultures during a 72-h period. In contrast, MMP-2 levels were significantly decreased in cisplatin-treated cells both in conditioned medium and cell extracts. However, no significant changes of MMP-2 levels were noted in BCNU-treated cells. Quantitative analysis of MMP-2 enzyme activity by densitometry and amount of MMP-2 protein by ELISA showed significantly decreased levels of MMP-2 in cisplatin-treated cells compared to BCNU and untreated glioblastoma cells. The results indicate that decreased levels of MMP-2 might represent an additional mechanism by which cisplatin provides its antineoplastic effects.
Clin Exp Metastasis 1997 Jul
PMID:Effect of cisplatin and BCNU on MMP-2 levels in human glioblastoma cell lines in vitro. 921 24

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5' end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.
Clin Exp Metastasis 1997 Jul
PMID:Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors. 921 33

Glioblastomas extensively invade the surrounding normal brain tissue, with a concomitant expression of various proteolytic enzymes, in particular urokinase-type plasminogen activator (uPA). In this study we used cis-diamminedichloroplatinum (cisplatin) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), commonly used anti-cancer drugs for the treatment of glioblastomas, to study the expression of uPA in three human glioblastoma cell lines in vitro. Cells were treated with 25 microM cisplatin and 50 microM BCNU, and uPA levels were estimated by fibrin zymography during a 72-h time course. Treatment of glioblastoma cells with cisplatin resulted in significantly decreased levels of uPA in serum-free conditioned medium and cell extracts, compared to BCNU-treated and untreated cell lines. Quantitative levels of uPA enzyme activity assessed by scanning laser densitometry and uPA protein by ELISA using antibody against uPA showed decreased levels of uPA in cisplatin-treated glioma cell lines relative to BCNU and untreated cell lines. Our results suggest that anti-tumor compound, cisplatin, may exert its anti-neoplastic effects by inhibiting uPA in malignant glioblastomas.
Clin Exp Metastasis 1997 Jul
PMID:Cisplatin but not BCNU inhibits urokinase-type plasminogen activator levels in human glioblastoma cell lines in vitro. 921 34

Cadherins are Ca(2+)-dependent cell adhesion molecules that play an important role in tissue formation and morphogenesis in multicellular organisms. In recent years, there have been reports of cadherin involvement in tumor invasion and metastasis. Twenty-two surgical specimens and some cultured cells were studied by immunohistochemical staining. No significant difference was observed in the patients with anaplastic astrocytoma, whereas decreased expression of N-cadherin was detected at the time of recurrence in those with glioblastoma. In these groups, cerebrospinal fluid dissemination was found, and contralateral cerebral metastases and extracranial metastases were observed. We conclude that decreased N-cadherin expression at the immunohistochemically demonstrated time of recurrence correlates with tumor invasion and dissemination of cerebrospinal fluid.
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PMID:Expression and role of cadherins in astrocytic tumors. 938 99

It is extremely rare for brain glioblastoma to metastasize extracranially. To elucidate whether glioblastoma cells remain non-metastatic when ectopically transplanted and CD44v gene is introduced, glioblastoma RG2-m cells were transfected with CD44v gene sequence encompassing v3-v10. After selection in culture medium with G418, CD44v expressing RG2-a cells were cloned. With RG2-a and its parental counterpart RG2-m, a series of experimental metastasis assays were performed in syngeneic F344 rats. When inoculated subcutaneously and in the foot-pad, both RG2-m and RG2-a cells metastasized spontaneously to the regional lymph nodes and lungs. However, metastasis of RG2-a was more severe and more organs were involved when compared to that of the parental RG2-m cells. The results indicate that glioblastoma becomes metastatic if extracranially transplanted and expression of CD44v would further enhance its metastatic patential.
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PMID:[Enhanced metastatic potential of rat RG2 glioblastoma cells transfected with CD44v (meta-1) sequence]. 938 71

We have performed immunohistochemical studies of mortalin in normal and tumor human brain sections. In normal brain sections, the expression was seen mainly as being confined to neurons. Normal astrocytes showed undetectable expression of this unique member of the heat shock 70 protein family. Three grades of astrocyte tumors (low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma), however, showed an increasing number of mortalin-positive cells. Other types of brain tumors, such as meningiomas, neurinomas, pituitary adenomas, and metastases, also showed elevated levels of mortalin expression compared to those in the normal brain. Mortalin has earlier been reported to have differential intracellular distribution in normal and transformed cells in vitro. Therefore, we substantiated the present study with immunofluorescence localization of the protein in normal and glioblastoma cells. The observations indicated that the tumors might be expressing a nonpancytosolic mortalin. An increase in number of mortalin-positive cells with malignant progression of brain tumors and its correlation with Ki-67 (a cell proliferation marker)-positive cells further suggested an involvement of nonpancytosolic mortalin(s) in malignant transformation of cells in vivo.
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PMID:Elevated levels of mortalin expression in human brain tumors. 941 64

CD44 belongs to a family of adhesion molecules displayed by a wide range of normal and malignant cells. Several studies implicated its presence as a marker for poor prognosis or metastases, especially in breast and colon cancer. CD44 has been proposed as an invasion marker for glioblastoma. We studied 75 astrocytic tumors with different degrees of anaplasia including juvenile pilocytic astrocytoma (JPA), low-grade astrocytoma (LGA), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM) to determine whether standard CD44 (CD44s) can be used as a clinically useful marker distinguishing between low- and high-grade gliomas. Archival paraffin-embedded tissues from 19 JPAs, 20 LGAs, 17 AAs, and 19 GBMs were immunostained with standard CD44 monoclonal antibody and compared with glial fibrillary acidic protein, using the streptavidin-complex peroxidase technique. Immunostaining was rated on a three-tiered scale by two observers. The expression of variant-splice forms of CD44 (CD44v) have been variably reported in brain tumors; a subset of these gliomas were tested with anti-CD44v monoclonal antibodies. In the tumors studied, 89% of JPAs, 90% of LGAs, 76% of AAs, and 84% of GBMs have 2+ or 3+ intensity for CD44s. Low- and high-grade gliomas showed no significant difference in staining (P > .05). Therefore, CD44s does not seem to correlate with the grading range of astrocytomas. The overall intensity of CD44s immunostaining usually, but not always, showed concordance with glial fibrillary acidic protein immunostaining, but the distinctive membrane staining of CD44s surface staining revealed fine cytologic detail in tumor cell processes in diagnostic sections. Some very anaplastic tumors were negative for CD44s, and gliomas were immunonegative for CD44v6. If variant chains (CD44v) are not found in gliomas and if this large series of low- and high-grade gliomas show no difference in CD44 expression, other factors must be explored to understand the differential behavior of low- and high-grade astrocytomas.
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PMID:CD44 expression in astrocytic tumors. 943 70

Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. They are divided into subclasses. The E- and P-cadherins are regarded as the epithelial subtype. Their expression has been demonstrated in many different carcinoma types. Using immunomorphological techniques, we studied the expression of E-cadherin in a series of 145 human brain tumours with the monoclonal antibody 5H9. Western blot analysis was used to confirm the immunohistochemical data. The tumour types represented were astrocytoma WHO I (n = 7), astrocytoma WHO II (n = 6), astrocytoma WHO III (n = 14), glioblastoma WHO IV (n = 8), oligodendroglioma WHO II (n = 5), ependymoma WHO II (n = 5), choroid plexus papilloma WHO I (n = 5), pineoblastoma WHO IV (n = 5), medulloblastoma WHO IV (n = 5), neurinoma WHO I (n = 5), meningioma WHO I and WHO III (n = 75) and pituitary adenoma WHO I (n = 5). Only choroid plexus papillomas (5/5) and meningiomas showed E-cadherin expression. In benign meningiomas (n = 45; 100%), positive E-cadherin immunoreactivity was found regardless of the histomorphological subtype. E-Cadherin was also expressed in 21 WHO I meningiomas (100%) invading dura, bone, brain, and muscle. In contrast, E-cadherin was absent from the majority of morphologically malignant meningiomas (6/9, 66.6%). In addition, in recurrent meningiomas (n = 9), E-cadherin expression in the recurrent tumours was identical to that in the primary neoplasm except in cases with malignant progression, where the malignant recurrent tumour was E-cadherin negative. In 2 cases of metastasizing meningiomas, no E-cadherin immunoreactivity was found in the primary tumours or their metastases.
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PMID:E-Cadherin in human brain tumours: loss of immunoreactivity in malignant meningiomas. 950 62


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