Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The p53 tumor-suppressor gene is the most commonly mutated gene in cancer. However, p53 gene alterations are infrequent in renal-cell cancer (RCC). Bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 and an inverse correlation between Bcl-2 expression and p53 mutation has been observed in breast cancer and glioma. To characterize the expression of bcl-2 in RCC and its relationship to the p53 status, we analyzed 25 RCCs by immunohistochemistry for Bcl-2 and p53, Southern hybridization for bcl-2, and PCR-SSCP and sequencing for p53. Positive Bcl-2 staining was detected in 17 of 25 RCCs, whereas positive p53 staining was seen in only 1. Amplification of bcl-2 or p53 mutation was not detected in any of the tumors. Bcl-2 protein was expressed in all 7 RCC cell lines examined. Only one of the 7 lines had p53 mutation. These results suggest that overexpression of bcl-2, rather than p53 mutation, may prevent apoptosis during RCC development.
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PMID:Frequent expression of Bcl-2 in renal-cell carcinomas carrying wild-type p53. 862 Dec 51

Current treatment for disseminated prostate cancer, whether progressive or hormone-resistant, do not improve survival. Insulin growth factors (IGFs) are potent stimulants of prostate epithelial cells growth, their presence having been demonstrated in high quantities in several tumours such as lung, hepatoma, pheochromocytoma, malignant glioma and breast cancer. Local management of growth factors production could improve the results of second line therapy in hormone-resistant prostate cancer. Levels of IGF-I were determined by radioimmunoassay (RIA) in normal (n = 5), hyperplastic (n = 5) and tumoral (n = 8) prostate tissue. Presence of IGF-I is confirmed in all tissues (9.62 +/- 5.81; 8.32 +/- 7.81 and 6.02 +/- 1.42 ng/mg protein, respectively) but no significant differences are displayed among the three groups.
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PMID:[Insulin growth factor I (IGF-I) in normal, hyperplastic, and tumor prostatic tissue]. 876 97

Manganese superoxide dismutase (MnSOD) has been previously shown to suppress the malignant phenotype of human melanoma and breast cancer cells. To test the possible role of MnSOD in glioma malignancy, MnSOD was overexpressed in wild type human glioma U118 cells and subcloned U118-9 cells by transfection of human MnSOD cDNA. The MnSOD-transfected cell lines demonstrated expression of exogenous (plasmid) MnSOD mRNA, increase in MnSOD immunoreactive protein, and a three- to eightfold increase in MnSOD enzymatic activity. The MnSOD overexpressing cell lines became less malignant as demonstrated by requiring a higher serum concentration to grow in vitro and much slower tumor growth in nude mice than the parental and neo control cell lines. These findings further support the hypothesis that MnSOD may be a tumor suppressor gene in a wide variety of human tumors.
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PMID:Suppression of the malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase. 905 45

A series of 120 pathologically verified intraspinal tumors was analyzed for the relative incidence and location of the tumors as well as the distribution of age and sex. These data were compared to series from Taiwan, mainland China, Thailand, Korea, Japan, Iran, India, and countries in the West. The ratio of brain to intraspinal tumors was about 5:1 in Taiwan, higher than those reported in China, Korea, and in the West. The male to female ratio is about six to five. For most tumors, male predominance is noted except for meningioma. The incidence of intraspinal tumors in the order of frequency is nerve sheath cell tumor(NSCT), metastatic tumors, meningioma, glioma, congenital tumors, and vascular tumors. In the East, the incidence of NSCT is about 40%, and meningioma is about 10%. In the West, they are both about 20%. Congenital tumors accounted for only 3.3%. In China, it was about 12% and this is the highest incidence of dysembryoplastic tumors in the world. Glioma has similar incidence (about 10%) in Taiwan, China, Thailand, Japan, and Iran (about 10%), whereas it is about 15% in the West and India. Korea has the highest incidence of glioma, (32.3%). Low incidences of metastatic intraspinal tumors (4.6-5.5%) were noted in China and Japan, but a higher incidence (14.2-24.2%) was seen in Taiwan, Iran, and the West. The most common metastatic tumors in the order of frequency is tumors of unknown origin, lung cancer metastasis, hepatoma, and breast cancer. The high percentage of unknown origin of metastasis may have resulted from loss of follow-up and lack of postmortem studies.
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PMID:An analysis of intraspinal tumors in south Taiwan. 917 84

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchyme-derived cytokine that stimulates motility and invasiveness of epithelial and cancer cells. These responses are transduced through the c-met proto-oncogene product, a transmembrane tyrosine kinase that functions as the HGF/SF receptor. We have shown that HGF/SF is a potent angiogenic molecule and that its angiogenic activity is mediated primarily through direct actions on vascular endothelial cells. These include stimulation of cell migration, proliferation, protease production, invasion, and organization into capillary-like tubes. We further showed that HGF/SF is overexpressed in invasive human cancers, including breast cancer, relative to non-invasive cancers and benign conditions. In invasive breast cancers, the content of HGF/SF is strongly correlated with that of von Willebrand's factor, a marker of vascular endothelial cells. Furthermore, transfection of breast cancer and glioma cell lines with HGF/SF cDNA greatly enhanced the ability of these cells to grow as tumours in orthotopic sites in syngeneic or immunocompromized host animals. The increased growth rate of the HGF/SF-transfected cells was attributable, in part, to increased tumour angiogenesis. These findings suggest that HGF/SF may function as a tumour progression factor, in part by stimulating tumour cell invasiveness and in part by stimulating angiogenesis.
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PMID:HGF/SF in angiogenesis. 952 73

A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer. PTEN/MMAC1 was also identified as the gene predisposing to Cowden disease, an autosomal dominant cancer predisposition syndrome associated with an increased risk of breast, skin and thyroid tumors and occasional cases of other cancers including bladder and renal cell carcinoma. We screened 345 urinary tract cancers by microsatellite analysis and found chromosome 10q to be deleted in 65 of 285 (23%) bladder and 15 of 60 (25%) renal cell cancers. We then screened the entire PTEN/MMAC1 coding region for mutation in 25 bladder and 15 renal cell primary tumors with deletion of chromosome 10q. Two somatic point mutations, a frameshift and a splicing variant, were found in the panel of bladder tumors while no mutation was observed in the renal cell carcinomas. To screen for homozygous deletion, we isolated two polymorphic microsatellite repeats from genomic BAC clones containing the PTEN/MMAC1 gene. Using these new informative markers, we identified apparent retention at the gene locus indicative of homozygous deletion of PTEN/MMAC1 in four of 65 bladder and 0 of 15 renal cell tumors with LOH through chromosome 10q. Identification of the second inactivation event in six bladder tumors with LOH of 10q implies that the PTEN/MMAC1 gene is occasionally involved in bladder tumorigenesis. However, the low frequency of biallelic inactivation suggests that either PTEN/MMAC1 is inactivated by other mechanisms or it is not the only target of chromosome 10q deletion in primary bladder and renal cell cancer.
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PMID:Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. 967 2

ErbB-4 is a recently described member of the epidermal growth factor receptor (EGFR) family which together with erbB-3 acts as a receptor for a group of ligands known as the neuregulins (NRGs) or heregulins (HRGs). Unlike the EGFR and erbB-2 relatively little is known about the expression of erbB-4 in human tumours. Using RT-PCR and Southern blotting analysis we have investigated the expression of erbB-4 mRNA in a range of human tumour cell lines and in normal and malignant breast tissue. Using primers which amplified a 658 base pair (bp) region corresponding to part of the cytoplasmic domain of c-erbB-4 we found the receptor was expressed in some but not all breast and ovarian tumour cell lines and also in a glioma cell line. The highest level of erbB-4 expression was found in the ovarian carcinoma OVCAR-3 and the breast carcinoma T-47D. In all cell lines where the 'full-length' erbB-4 was detected, a second previously undescribed c-erbB-4 sequence was also found as a 610 bp PCR product. The alternative PCR product was identical in sequence to c-erbB-4 except for a deletion of 48 bp which encodes a consensus phosphatidylinositol 3-kinase (PI3K) binding site. This suggested that the two forms of erbB-4 might interact with different intracellular signalling pathways and therefore influence a wider variety of cellular responses to heregulin than previously thought. Expression of both erbB-4 variants was found in 7/7 normal breast tissues but only in 9/12 breast tumours analysed. In line with the terminology of Elenius et al. (1997b) we have designated the two isoforms of the C-terminal transcripts as CT-a (full-length) and CT-b which lacks the P13K binding motif. These results identify suitable cell lines for the further investigation of erbB-4 expression and function and suggest that the role of erbB-4 in breast cancer warrants further investigation with larger numbers of normal and malignant breast tissues.
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PMID:Two erbB-4 transcripts are expressed in normal breast and in most breast cancers. 978 9

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.
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PMID:A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood. 981 90

Technetium-99m sestamibi (MIBI), an alternative radiopharmaceutical for myocardial perfusion imaging, has also been proposed for use as an imaging agent for various tumours, including breast cancer, lung cancer, lymphomas, melanomas and brain tumours. After routine radiation therapy, deteriorating clinical status or treatment failure may be due to either radiation-induced changes or recurrent tumour. Computed tomography and magnetic resonance imaging offer imperfect discrimination of tumour viability and radionecrosis. Against this background we undertook a retrospective study of 35 malignant glioma patients in whom clinical deterioration had occurred, in order to clarify the value of 99mTc-MIBI SPET in identifying tumour recurrence. SPET was performed 15 min after intravenous injection of 1110 MBq with a dual-headed gamma camera using a fan-beam collimator. Transverse, coronal and sagittal views were reconstructed. Intense MIBI uptake was found in 31 patients. This uptake was correlated with tumour recurrence as proved by histology and/or rapid, fatal evolution of these cases. The statistical analysis performed on this population of patients with MIBI uptake revealed a group of patients with a long mean survival and a group with a short mean survival. Two subgroups were found within each of these groups, according to the functional index ratio (tumour uptake/pituitary gland uptake ratio). No MIBI uptake was found in four patients who are still alive and can be considered to be disease-free. In those cases showing MIBI uptake, death occurred an average of 6.69 months following brain SPET. According to our results, the specificity and sensitivity of 99mTc-MIBI brain SPET seem to be high. Moreover, this technique is more accurate than computed tomography or magnetic resonance imaging for discriminating between tumour recurrence and radionecrosis.
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PMID:Technetium-99m sestamibi brain single-photon emission tomography for detection of recurrent gliomas after radiation therapy. 987 Oct 97


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