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)

We report two patients with leptomeningeal metastatic disease, one from breast cancer and the other from a spinal cord glioma, who developed episodic elevated intracranial pressure (ICP), each episode accompanied by the gradual onset of severe spine and radicular pain. Symptoms of pain promptly and completely resolved with opening of the on-off valve of each patient's ventriculoperitoneal shunt. It is theorized that the patients' radicular pain was caused by nerve root ischemia secondary to elevated ICP.
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PMID:Radicular pain can be a symptom of elevated intracranial pressure. 1010 41

p53 deficient mice have been found to be highly prone to develop tumors spontaneously. In particular, the thymic lymphoma was observed predominantly, which is not the case for p53-related tumorigenesis in human. To elucidate this differences, I tried to rescue the p53 deficient mice from lymphoma originated in thymus by allowing the p53 expression in their lymphocytes by using transgenic technique. They survived longer than the p53 deficient littermates. In addition, they developed various types of tumors including glioma, medulloblastoma and breast cancer, which have not been observed in p53 deficient mice.
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PMID:[Tissue specific rescue of lymphomas arose various types of tumors with p53-deficiency]. 1033 29

Some of the psychotropic agents widely used for the amelioration of anxiety, depression, and psychosis also show an effect at the cellular proliferation level. Surprisingly little research, however, has been directed to the antitumoral potential of these drugs, alone or in combination with established cancer treatments. Our review of the literature to date has yielded some promising early findings. Ligands active at the benzodiazepine (BZ) receptors have been studied the most extensively and were found to have differential, concentration-dependent effects on the growth and proliferation of both normal and cancer cells. Of the phenothiazines tested, chlorpromazine (CPZ) and perphenazine (PPZ) had the most potent cytotoxic action on fibroblasts and glioma cells. Antiproliferative effects also were noted by these and other agents in leukemic and breast cancer cell lines. Additional psychotropic drugs studied include the atypical antipsychotics, antidepressants, and mood stabilizers, especially lithium. Most of the reported activities were observed in in vitro studies and were achieved at high pharmacological concentrations. Further in vivo studies in well-designed animal models are warranted to determine whether these well-tolerated, relatively inexpensive, and widely available drugs or their derivatives may be added in the future to the armamentarium of cancer pharmacotherapy.
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PMID:Effects of psychotropic drugs on cell proliferation and differentiation. 1048 24

Anthracyclines are effective in breast cancer and have in vitro cytotoxicity in glioma. In patients with glioma anthracyclines are not effective possibly because the hydrophilic drugs do not reach cytotoxic levels in tumor tissue. Idarubicin is more lipophilic than the other anthracyclines and is more cytotoxic in glioma cell lines. The uptake of idarubicin and its major metabolite idarubicinol in brain tumor tissue were measured in a patient with a brain metastasis from breast cancer and in 4 patients with malignant glioma after an oral dose of idarubicin (45 mg/m2 in 1 patient; 25 mg/m2 in 4 patients), given 15-24 h before brain tumor resection. The concentrations of idarubicin and of idarubicinol in tumor tissue exceeded the concurrent plasma concentrations as well as the peak plasma concentrations in all cases. The median tumor:concurrent plasma ratio of idarubicinol was 5.7 (range 1.7-18). The concentration of idarubicinol in the marginal zone between brain and tumor tissue was lower than in central tumor tissue, but was still higher than the plasma concentration in 2 of the 3 examined cases. Bone marrow suppression (platelets CTC grade 2, granulocytes CTC grade 4) occurred after a single dose of 45 ml/m2. No toxicity was seen at a dose of 25 mg/m2. These results, the in vitro activity of idarubicin in glioma, the convenience of oral administration, and its toxicity profile make clinical studies with idarubicin in malignant glioma, and perhaps also in brain metastases from breast cancer worthwhile.
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PMID:Penetration of idarubicin into malignant brain tumor tissue. 1058 71

Central nervous system (CNS) tumors are the most common solid neoplasms in children. Medulloblastomas (MEDs) resemble embryonic neuroectodermal stem cells and their immature, uncommitted neuronal and glial progeny. Apoptosis is a basic physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally, disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) receptor (FasR) and programmed or active cell death (PCD) was studied in childhood MEDs with varying stages of malignancy, and cell differentiation features. The majority of neoplastically transformed, neuroectodermal in origin cells, particularly in MEDs, express FasR, whereas normal cells in the CNS do not. FasR is a transmembrane glycoprotein, which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within childhood PNETs/MEDs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with anti-section i FasR antibodies. The resence of FasL has also been detected in childhood glial tumors. Therefore, a spontaneous, cellular immunophenotype (IP) regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood brain tumors during neoplastic growth and progression. During our systematic immunocytochemical screening, we employed formalin fixed, paraffin-wax embedded tissue sections, as well as frozen sections of 34 primary human childhood PNETs/MEDs. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique, modified by us, provided excellent immunocyto-chemical results. A systematic observation of the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"-the highest possible; number of stained neoplastic cells: +3 to +4, between 50% to 90%) of FasR, was detected employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colon epithelium. Certainly, the coexpression of FasR, FasL, and other PCD-related proteins have also been reported in other human malignancies: breast cancer, colorectal carcinomas, large granular lymphocytic leukemia of T or NK cell origin, melanomas, lung, prostate, pancreas, and hepatocellular carcinomas. The coexpression of both FasR and FasL on several neoplastic cell types may represent an effective mechanism for tumor escape of the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching their signal transduction from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) represents a new and exciting immunotherapeutical possibility in the treatment of primary childhood neuroectodermal tumors.
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PMID:Fas (APO-1, CD95) receptor expression and new options for immunotherapy in childhood medulloblastomas. 1065 26

Estrogens influence differentiation, growth and function of neurons, but less is known of their effects on glia. In our experiments reported here, the ovarian steroid, 17beta-estradiol, and the "designer", non-steroidal estrogen, tamoxifen, effectively protected C-6 glioma 2B clone cells from the cytotoxicity of the excitatory neurotransmitter, glutamate. Exposure of these cells to 10-20 mM glutamate induced 61-78% cell death. Pre-treatment of the cells with 0.01 mM estradiol or with 2 microM tamoxifen significantly reduced the glutamate-induced cell death, estradiol being the most effective in this regard. Estradiol- or tamoxifen-treated cells that had survived glutamate damage appeared more mature than controls. Thus, estrogens often used in therapy (estradiol as replacement after menopause and tamoxifen for treatment/prevention of breast cancer) may significantly protect glial cells against glutamate toxicity and stimulate cell differentiation.
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PMID:Protective action of 17beta-estradiol and tamoxifen on glutamate toxicity in glial cells. 1071 83

Impaired function of apoptosis-related genes is deeply involved in oncogenesis and the progression of cancers, and caspase-3 plays a critical role as an executioner of apoptosis. We introduced the caspase-3 gene via an adenovirus (Adv) vector into Alexander hepatoma cells, MCF-7 breast cancer cells, and U251 and U-373MG glioma cells which have different endogenous levels of caspase-3 expression. None of the cell lines underwent apoptosis by overexpression of caspase-3, indicating that induction of caspase-3 alone is not applicable for cancer gene therapy. Next, we investigated whether overexpression of caspase-3 could enhance Fas ligand-mediated apoptosis in these four cell lines. In U-373MG cells, which showed the highest level of expression of surface Fas among the four cell lines, coinfection of the Adv for caspase-3 (Adv-caspase-3) and the Adv for Fas ligand (Adv-FL) induced a remarkably increased degree of apoptosis compared with that induced by the single infection of either Adv-caspase-3 or Adv-FL. Similar results were obtained by cotreatment with anti-Fas antibody in U-373MG cells. These data suggest that when strong proapoptotic upstream stimuli are induced, the level of caspase-3 expression determines the degree of apoptosis in cancer cell lines. In conclusion, overexpression of caspase-3 alone did not induce apoptosis in cancer cells. Both a strong proapoptotic signal and a high expression of caspase-3 were required to induce drastic apoptosis in cancers. This strategy would be highly beneficial for selected cancer patients.
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PMID:Adenovirus-mediated transfer of caspase-3 with Fas ligand induces drastic apoptosis in U-373MG glioma cells. 1077 15

The antiestrogen tamoxifen is commonly used to treat breast cancer, but it also has therapeutic activity in several other types of cancer. Many of these tumors, including malignant gliomas, are estrogen receptor negative. Nonetheless, high concentrations of tamoxifen can directly reduce cell proliferation in some of these tumors and induce apoptosis. In this study, the role of tamoxifen in calcium signaling and calcium-induced cell death was studied in both malignant glioma cell lines and MCF-7 breast cancer cells. Tamoxifen potently increased the spatial expansion of calcium waves by 30-150% while significantly enhancing and prolonging agonist-induced calcium elevations. Furthermore, tamoxifen pretreatment accelerated calcium ionophore-induced death by more than 20 min, suggesting that tamoxifen lowered cellular resistance to calcium loads. In contrast to its potentiating of calcium signaling in tumors, tamoxifen had no significant effect on calcium signaling in cultures of primary astrocytes from either human or rat brain. This study demonstrates the existence of calcium signaling in breast cancer and glioma cells and identifies tamoxifen as a potential modulator of tumor-associated calcium signaling.
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PMID:Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells. 1103 78

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.
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PMID:Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer. 1123 78

H11 is a human IgM monoclonal antibody which recognizes a novel tumour-associated antigen expressed on melanoma, glioma, breast cancer, colon cancer, prostate cancer, lung cancer and B-cell lymphoma. In this study, a recombinant single-chain Fv (scFv) fragment of H11 labelled with 111In was investigated for tumour imaging in athymic mice implanted subcutaneously with A-375 human melanoma xenografts. H11 scFv was derivatized with diethylenetriaminepentaacetic acid (DTPA) for labelling with 111In. The immunoreactivity of DTPA-H11 scFv against A-375 cells in vitro ranged from 23% to 36%. 111In-DTPA-H11 scFv was rapidly eliminated from the blood and most normal tissues (except the kidneys) reaching maximum tumour/blood ratios of 12:1 at 48 h post-injection. Tumours were imaged as early as 40 min after injection. The kidneys accumulated the highest concentration of radioactivity (up to 185% injected dose/g). Tumour uptake was 1-3% injected dose/g. The whole-body radiation absorbed dose predicted for administration of 185 MBq of 111In-DTPA-H11 scFv to humans was 37 mSv. The radiation absorbed dose estimates for the kidneys, spleen and intestines were 405 mSv, 698 mSv and 412 mSv, respectively. The results of this preclinical study and a concurrent phase I trial suggest a promising role for H11 scFv for tumour imaging.
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PMID:Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with 111In. 1138 83


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