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)

Although human glioblastomas are highly invasive tumors intracerebrally, only rarely do they metastasize outside the central nervous system. In contrast, the brain is a major target for metastatic spread of many systemic tumors. Recently, it was demonstrated that expression of splice variants of CD44 (CD44v), but not standard CD44 (CD44s), was sufficient to confer metastatic potential to low- or nonmetastatic rat tumor cells. Because CD44 is expressed in brain tumors, we examined whether differential expression of CD44 isoforms was correlated with the metastatic behavior of these tumors. We compared CD44s and CD44v expression in 17 human glioblastomas, 18 glioma cell lines, and metastases of 15 other tumors to the brain by reverse transcription/polymerase chain reaction, Northern blotting, and immunocytochemistry. These experiments showed that 0 of 17 glioblastomas and 0 of 18 glioma cell lines expressed CD44v as compared to 12 of 15 brain metastases. These data show a correlation between CD44v expression and the metastatic ability of the tumors analyzed (P < 0.01). This suggests (a) that the biological significance of the lack of CD44v expression in human glioblastomas warrants further examination with regard to their inability to metastasize extraneurally and (b) that CD44v expression may play a role in the intracerebral spread of about 80% [corrected] of the brain metastases. Therefore, CD44v expression should be further considered as a potential marker for differential diagnosis and prognosis of patients with brain metastases.
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PMID:Variant CD44 adhesion molecules are expressed in human brain metastases but not in glioblastomas. 769 37

Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.
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PMID:Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat. 775 74

A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor alpha, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
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PMID:A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. 776 95

CT findings of 2 patients with primary cerebral lymphoma were presented with a literature review of the CT manifestations of primary cerebral lymphoma. On the plain CT scan, most of lymphomas were either hyper- or isodense, well demarcated, and had variable surrounding edema. The tumors were mostly situated in the deep structures of brain: the basal ganglia, corpus callosum, periventricular white matter and vermis of cerebellum. On the postcontrast CT scan, cerebral lymphomas showed a homogeneous contrast enhancement. Ring enhancement, occasionally gyral enhancement also may be seen. On the CT scan, primary cerebral lymphomas were usually misdiagnosed as glioma, meningioma, metastases and abscess. The difference between lymphoma and the above lesions was discussed.
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PMID:[CT diagnosis of primary cerebral lymphoma--report of 2 cases]. 780 5

Degradation of the extracellular matrix is a prerequisite for acquisition of the invasive phenotype. Several proteinases released by invading tumor cells appear to participate in the focal degradation of extracellular matrix proteins. Using an enzyme-linked immunosorbent assay, enzymatic assays, Western and Northern blotting techniques, we determined whether increased levels of the cysteine protease cathepsin B correlated with the progression and invasion of human gliomas. The amount of cathepsin B activity and protein content were highest in glioblastomas, lower in anaplastic astrocytomas and lowest in normal brain tissue and low-grade gliomas. There were significantly higher amounts of M(r) 25,000 and 26,000 bands in glioblastoma and anaplastic astrocytoma than in normal brain and low-grade glioma tissue extracts as determined by Western blotting with anti-cathepsin antibodies. In addition, cathepsin B transcripts were overexpressed in anaplastic astrocytoma (about two- to three-fold), in glioblastoma (about eight- to 10-fold), compared with normal brain tissue and low-grade glioma. Immunohistochemical staining for cathepsin B showed intense immunoreactivity in tumor and endothelial cells of glioblastomas and anaplastic astrocytomas but only weak immunoreactivity in low-grade glioma and normal brain tissues. Therefore, we conclude that cathepsin B expression is greatest in highly malignant astrocytomas, especially in glioblastomas, and is correlated with the malignant progression of astrocytomas.
Clin Exp Metastasis 1995 Jan
PMID:Overexpression and localization of cathepsin B during the progression of human gliomas. 782 Sep 56

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

In 16 patients with 21 metastatic brain tumors and 9 patients with a malignant glioma, tumor volume, volume of the edematous tissue, edema production, speed of edema propagation and edema resolution were examined by using the CT. Edema production was determined according to a technique described previously and ranged between 0.09 and 1.63 ml/h in metastases and between 0.42 and 3.49 ml/h in gliomas. The speed of edema propagation ranged from 0.2-2.2 mm/h. Edema resolution can take place within the tissue (i.e. reabsorption into blood) as well by drainage into the ventricular or subarachnoid CSF. In a few small metastases with a small perifocal edema (without contact to the ventricule or the subarachnoid space) the amount of edema resolution within the tissue could be determined and averaged 0.0086 ml/h/cm3. This probably represents the reabsorption of edema fluid into capillaries within the edematous tissue. If this value is used to calculate the edema reabsorption in larger tumors, the resulting data are considerable lower than the respective edema production rate of that tumor. This indicates, that in larger tumors the main fraction of the edema fluid is draining into the ventricular and/or subarachnoid CSF.
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PMID:Formation and resolution of human peritumoral brain edema. 797 93

Fotemustine is a new chloroethylnitrosourea characterized by the grafting of a phosphonoalanine group onto a nitrosourea radical. Clinical studies using fotemustine have been conducted in malignant glioma, brain metastasis of non-small cell lung cancer, and disseminated malignant melanoma. In recurrent malignant glioma, fotemustine has been used as a single agent: assessed by computed tomography scan, after 8 weeks, the objective response rate was 26.3% among 38 evaluable patients. Median duration of response was 33 weeks. The main toxicity was hematological (thrombocytopenia and leucopenia). A trial with high-dose fotemustine and autologous bone marrow rescue in newly diagnosed glioma was conducted in 26 patients, and 6 showed a partial response. The median overall survival was approximately 11 months. Myelosuppression was noted in all patients except 1, and other toxicity reported was central nervous system toxicity and epigastric pain. Combined with radiotherapy in 55 patients, a 29% response rate was observed, and this combination was well tolerated and easily manageable on an outpatient basis. Finally, fotemustine has been used intraarterially, with 10 objective responses observed among 26 evaluable patients. In brain metastases of non-small cell lung cancer, fotemustine proved to be active with a response rate of 16.7%. Combined with cisplatinum, fotemustine is still under study, but preliminary results are promising. In cerebral metastases of disseminated malignant melanoma, fotemustine has been evaluated in a total of 140 patients in the various studies: median response rate is 24.3%, ranging from 8.3% to 60.0%. Fotemustine appears to be a good candidate in the treatment of primary brain tumors and metastases.
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PMID:Fotemustine in the treatment of brain primary tumors and metastases. 803 64

Metalloproteinases, inhibitors of metalloproteinases, plasminogen activators, inhibitors of plasminogen activators and cathepsins are thought to be involved in invasion by tumor cells. Glioblastoma multiforme is highly malignant and extremely refractory to therapy. One reason is because of its highly invasive nature within the nervous system. However, it remains unclear how invasion/dissemination of glioblastoma multiforme proceeds. In this study, we attempted to determine which proteinases were responsible for the invasion activity of human glioma cell lines in vitro. Nine human glioma cell lines (NHG1, NHG2, IN157, IN301, IN500, U251, U343, T98G and CCF-STTG1) derived from patients with glioma were grown in culture and used. We compared the invasion activity of glioma cell lines in a Matrigel invasion assay system, and formulated the activity as invasion index (%). Among the nine cell lines, IN157, IN500 and U343 showed less than 10% invasion activity (low group); NHGI, IN301 and CCF-STTG1 showed 10-25% activity (intermediate group); NHG2, U251 and T98G showed more than 30% activity (high group). Addition of an inhibitor of metalloproteinases, TIMP-1, to the assay system was found to significantly inhibit invasion activity of T98G cells (P < 0.01). Northern blot analysis demonstrated expression of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and PA inhibitor-1 (PAI-1) in some of the above cell lines. Cellular levels of PAs and their inhibitor mRNA, however, appeared not to be correlated with invasion activity in most glioma cell lines except for CCF-STTG1. Expression of 72 kDa type IV collagenase (MMP-2) was much lower in IN157, IN500 and U343 than other cell lines, whereas expression of TIMP-1 was much higher in IN500 than in other cell lines. Zymographic activity was found to be comparable to MMP-2 mRNA levels in all cell lines except for CCF-STTG1. Type IV collagenolytic activity was also comparable to invasion activity in nine cell lines. These observations suggest the role of type IV collagenase and its inhibitors in determining capacity for invasion by human gliomas. However, a comprehensive analysis both in vitro and in vivo is required to confirm the role for this enzyme in glioma cell invasiveness.
Clin Exp Metastasis 1994 Jul
PMID:Expression of 72 kDa type IV collagenase and invasion activity of human glioma cells. 803 4

More than 80% of malignant gliomas have been reported to recur locally after conventional chemoradiation therapy. This regional pattern of recurrence has encouraged the introduction of new treatments for local tumors. Since 1987 interstitial brachytherapy using Iridium-192 seeds has been carried out in our department for malignant brain tumors. The present study was designed to evaluate the patterns of recurrence following interstitial brachytherapy and to assess how this recurrence differs from that observed in patients treated by conventional means. Ten patients who satisfied the following criteria were selected among 41 patients treated with brachytherapy. The criteria were; 1) histologically diagnosed to be malignant glioma (astrocytoma grade III or glioblastoma), 2) followed up with MRI every month after the brachytherapy, 3) follow-up period was more than 6 months, and 4) the time of recurrence was confirmed. The patients were classified into 3 groups according to the patterns of tumor recurrence as follows; 1. Local recurrence group: The tumor recurred near the pretreatment tumor site. 2. Necrotomy group: Reoperation was performed because of neurological deterioration and radiographic evidence of increasing mass effect with surrounding edema. Neurological symptoms were unchanged or improving during the 6 months after the reoperation. 3. CSF seeding group: Primary tumor was well controlled, but seeding via cerebrospinal fluid was recognized on MRI. Local recurrence occurred in three patients, necrotomy was carried out in three patients, and CSF metastases were defined by both MRI and clinical symptoms in four patients. Median radiation does was 33 Gy in the local recurrence group, 57.6 Gy in the necrotomy group, and 43.2Gy in the CSF seeding group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Patterns of recurrence in malignant gliomas after brachytherapy]. 816 95


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