Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue inhibitors of metalloproteinases (TIMPs) are negative regulators of matrix metalloproteinases (MMPs) which degrade major components of the extracellular matrix. The aberrant expression of TIMPs is believed to represent an important modulating factor in the invasive capacity of human tumors. In the present study we analyzed the expression of TIMPs in human brain tumor tissue samples by an enzyme-linked immunosorbent assay (ELISA) and by Northern blotting analysis. Quantitation of TIMP-1 and TIMP-2 by ELISA demonstrated low levels of TIMP-1 and TIMP-2 proteins in glioblastomas, and moderate levels in anaplastic astrocytomas compared with normal brain tissues low-grade gliomas and metastatic tumors (renal and breast carcinomas and melanomas). Northern blot analysis of TIMP-1 transcripts demonstrated higher expression in meningioma, normal brain tissues and other metastatic tumors than in anaplastic astrocytoma and glioblastoma. Two distinct transcripts of 1.0 and 3.5 kb were observed for TIMP-2 mRNA in normal brain tissue and in tumor extracts. In addition, TIMP-2 mRNA expression was lower in glioblastoma and anaplastic astrocytoma than in meningioma, normal brain tissues and metastatic tumors. These findings suggest that down-regulation of both TIMP-1 and TIMP-2 contributes significantly to the invasive potential of human glioblastoma multiforme and anaplastic astrocytomas.
Clin Exp Metastasis 1995 Jan
PMID:Expression of tissue inhibitors of metalloproteinases: negative regulators of human glioblastoma invasion in vivo. 782 Sep 57

A case history of the multifocal brain glioma in 13-year-old girl is reported. Numerous neoplasmatic foci were found using MRI within the vermis and cerebellar hemisphere and, later, also within the brain stem, cervical spinal cord and both brain hemispheres. Bioptical examination of the tumors revealed the structure of anaplastic astrocytoma with oligodendromatous component. The authors suggest that the foci may be considered as multiple metastases from the primary cerebellar astrocytoma and the neoplastic cells might have been transported within CNS through cerebrospinal fluid.
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PMID:Multifocal central nervous system glioma--a case history. 788 38

Between February 1993 and March 1994, 75 metastases, 16 gliomas and 2 AIDS-related malignant lymphomas were treated with Gamma Knife radiosurgery. Metastatic brain tumors (54% lung cancer, 14% breast cancer, 13.5% melanoma) were the most frequent and clinically rewarding cases. So-called local control was achieved in almost all patients, the vast majority showing neurological improvement associated with radiological disappearance or dramatic shrinkage of the tumor within 9-12 weeks from treatment. According to our modified 'Pittsburgh' protocol, we have treated up to four distinct intracranial lesions, up to a total maximum volume of 20 cm3, with an average surface dose of 25 Gy, with or without additional whole brain radiotherapy (WBR). Preliminary follow-up data seem to confirm increased quality of life and survival rates. The results were particularly striking whenever primary tumors were under control, and were poorly influenced by associated WBR. Gamma Knife treatment was also performed in a selected group of patients with small-to-medium-sized, well-defined, histologically proven, cerebral gliomas. The main indications for radiosurgery were high-risk surgery, multifocal disease, ventricular seeding and unresected or recurrent tumor. The prescription doses ranged from 18 to 30 Gy, with a mean of 27 Gy. Low-grade astrocytomas (9/16 cases) showed the better clinical and radiological response to treatment, with neurological recovery and significant reduction in tumor volume within 3-5 months in 5 of the 9 patients. In 4 of 7 high-grade gliomas, there was little or no response. However, an impressive radiological regression with full clinical recovery was observed in 2 high-grade cases with small tumor volumes: a recurrent, anaplastic 'mixed glioma' of the pineal region and a double ventricular seeding of a previously operated anaplastic astrocytoma.
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PMID:Gamma Knife radiosurgery of primary and metastatic malignant brain tumors, a preliminary report. 858 40

Although survivals of infants with malignant brain tumors are worse than any other age group, one possible exception to this rule are the malignant gliomas. Eighteen children less than 3 years of age with malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma and malignant glioma) were treated on the Pediatric Oncology Group regimen of prolonged postoperative chemotherapy and delayed irradiation, (1986-1990). Of 10 children evaluable for neuroradiologic response, 6 had partial responses (> 50% reduction) to two cycles of cyclophosphamide and vincristine. Progression free survivals at 1,3 and 5 years were 54.25% +/- 12, 43% +/- 16 and 43% +/- 23 respectively. Survivals at 5 years were 50% +/- 14. Four children were not irradiated after 24 months of chemotherapy due to parental refusal and none have developed recurrent disease. Neither degree of surgical resection, presence or absence of metastases, nor pathology influenced survival but this may reflect small sample size. This study suggests that some malignant gliomas in infants are chemotherapy sensitive and may be associated with a good prognosis. Why infants with these high-grade gliomas fare better than adults is not clear. It is likely that there is something intrinsically different about them that cannot be identified on routine pathologic examination.
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PMID:Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. 883 66

Increased levels of human cysteine proteases have been implicated in the progression of tumors from the premalignant to the malignant state. The physiological activities of these proteases are regulated by their interactions with specific inhibitors. To our knowledge there have been no previous reports about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study reported here, we determined CPI activity during glioma progression and compared that with normal human brain tissue. We also determined CPI activities in meningioma and glioblastoma cell lines in vitro. This activity was significantly higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma and glioblastoma. CPI activity was significantly higher in benign and atypical meningioma cell extracts in comparison with those from malignant meningiomas and with those from glioblastoma cell lines. After several passages, one benign meningioma cell line showed reduced levels of CPI and increased levels of cathepsin. Our results suggest that decreases in the activities of CPI may contribute to the malignant properties of brain tumors.
Clin Exp Metastasis 1996 Sep
PMID:Expression of cysteine protease inhibitors in human gliomas and meningiomas. 887 8

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

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

Despite surgery and adjuvant cytotoxic therapy anaplastic astrocytoma, glioblastoma and diffuse intrinsic brain stem glioma continue to have dismal prognosis. Differentiation induction is a new approach taking into account that malignant glioma cells share many features with immature glial progenitor cells that are capable of terminal differentiation. The concept of differentiation therapy is currently evaluated for several pediatric malignancies with or without multimodal standard therapy. Valproic acid (VPA) is a branched chain fatty acid that is able to inhibit proliferation of neuroectodermal cells and to induce these cells along neuronal or glial lineage. Preclinical studies have shown that VPA inhibits growth of human and rodent glial tumor cells in vitro and induces a distinct mature glial phenotype. In addition, growth of human neuroblastoma cells is inhibited in vitro and in vivo and exhibits marked evidence of differentiation. Treatment of neuroblastoma and glioma cells with VPA was accompanied by changes of surface molecule expression that enhance immunogenicity and reduce their capability to metastasize. The antitumoral effects observed in preclinical studies were reached at concentrations that are readily achieved in patients treated with VPA for epilepsy. Epilepsy patients receiving VPA have significantly enhanced hemoglobin F levels, supporting the hypothesis that nontoxic levels of VPA can induce cellular differentiation. Broad clinical experience with VPA and its low toxicity encourage the evaluation of VPA in patients that have been submitted to postoperative combined chemo- and radiotherapy for pediatric malignant glioma.
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PMID:Valproic acid for the treatment of pediatric malignant glioma. 1047 71

An 11-year-old entire female German shepherd dog was presented with a progressive non-painful exophthalmos of the right eye. Ultrasonographic examination revealed a solid and well-defined orbital mass compressing the globe. Thoracic radiography revealed multiple pulmonary metastases of different sizes. The histopathological and immunohistochemical features of both the retrobulbar tumour and pulmonary metastases were consistent with an anaplastic astrocytoma. This represents an unusual case of an extracranial astrocytoma with multiple pulmonary metastases. The clinical features and the ultrasonographic, histopathological and immunohistochemical findings are described.
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PMID:Retrobulbar anaplastic astrocytoma in a dog: clinicopathological and ultrasonographic features. 1100 38


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