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)

OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response. Here, we newly generated two specific mouse antihuman OX40 monoclonal antibodies (mAbs) (2G2 and 1F7), whose specificities are quite different from the available OX40 mAb (ACT35) by competition assay. It was also found that both mAbs could enhance the proliferation, activation and differentiation of T lymphocytes primed by anti-CD3 mAb. These results evidenced that both were functional antihuman OX40 mAbs. Furthermore, stained by 2G2 and 1F7, FCM and immunohistochemistry detected the constitutive expression of OX40 on tumor cell lines from epithelium, breast cancer and glioma tissues. Meanwhile, the non-tumor tissues (thyroid gland, stomach gland) were also found OX40 expression. These results suggested that OX40 is not only expressed in activated T cells, but also in some tumors as well as normal gland tissues. Such expression pattern indicated that OX40 may be a valuable surface antigen in unveiling its expression and function outside the immune system. Briefly, these novel antibodies may contribute to the evaluation of the mechanism of tumor metastasis and eventually shed light on further study of tumor immunotherapy and autoimmune diseases.
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PMID:Characterization and application of two novel monoclonal antibodies against human OX40: costimulation of T cells and expression on tumor as well as normal gland tissues. 1663 67

Neoangiogenesis is required for tumor development and progression. Many solid tumors induce vascular proliferation by production of angiogenic factors, prominently vascular endothelial growth factor (VEGF). Because nutrition is a causative factor for tumor prevention and promotion, we determined whether secondary plant constituents, i.e., flavonoids, tocopherols, curcumin, and other substances regulate VEGF in human tumor cells in vitro. VEGF release (concurrent with synthesis) from MDA human breast cancer cells and, for comparison, U-343 and U-118 glioma cells was measured by ELISA. Of 21 compounds tested, 9 showed significant inhibitory activity at 0.1 micromol/L in MDA human breast cancer cells. The rank order of inhibitory potency was naringin > rutin > alpha-tocopheryl succinate (alpha-TOS) > lovastatin > apigenin > genistein > alpha-tocopherol >or= kaempferol > gamma-tocopherol; chrysin and curcumin were inactive except at a concentration of 100 micromol/L. Glioma cells were similarly sensitive, with U343 more than U118, especially for alpha-TOS and tocopherols. Among the tocopherol derivatives, alpha-TOS (0.1 micromol/L) was the most effective in reducing VEGF release. Overall, the glycosylated flavonoids (i.e., naringin, a constituent of citrus fruits, and rutin, a constituent of cranberries) induced the greatest response to treatment at the lowest concentration in MDA human breast cancer cells. Inhibition of VEGF release by flavonoids, tocopherols, and lovastatin in these models of neoplastic cells suggests a novel mechanism for mammary cancer prevention.
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PMID:Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. 1670 7

We developed a molecular imaging agent (MIA), a conjugable form of PK11195 (conPK11195) coupled to a lissamine dye (Liss-ConPK11195), which targets the peripheral benzodiazepine receptor (PBR). To determine that our compound specifically binds to this 18 kDa protein, primarily expressed on the mitochondria, we performed classic binding studies on live MDA-MB-231 breast cancer cells and measured fluorescence in cell fractions of C6 glioma cells. We found that conPK11195 conjugated to the fluorophore retained significant binding to its target. Here we demonstrate the utility of the agent for in vitro imaging of live cells by specific binding to the protein of interest.
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PMID:A peripheral benzodiazepine receptor targeted agent for in vitro imaging and screening. 1670 12

The prognosis for patients with either a primary or metastatic brain tumor is poor. Clearly new forms of therapy to improve the long-term survival of patients with malignant brain tumors are urgently needed. The authors are in the process of developing a new and novel form of treatment for primary and metastatic brain tumors in which they use genes involved in growth repression. In particular most tumors fail to induce an antitumor immune response strong enough to kill the tumor. Under appropriate circumstances, however, immunity can be produced in unique structures on the tumor cells known as antigens. To prepare the vaccine, genes are transferred into a fibroblast cell line that causes the cell to produce cytokines, the potent proteins known to stimulate the immune system. These cells are subsequently injected into the tumor bed, resulting in the development of an antitumor immune response. In experiments described in this manuscript, the authors have investigated a number of ways of augmenting the immune response by administering this type of cellular vaccine. They found that mice with a primary intracerebral glioma, melanoma, or breast cancer treated with this allogeneic cytokine-secreting vaccine survived significantly longer than untreated mice. Additionally the vaccine was found to stimulate a systemic antitumor immune response, as shown by immunocytotoxic studies, histopathological examination, and delayed immune memory responses. In summary, these results indicate that immunogene therapy is a promising new targeted therapy for the treatment of intracerebral malignant tumors.
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PMID:Cytokine immunogene therapy. 1681 85

2-Fluoro-4-nitrophenol-beta-D-galactopyranoside (OFPNPG) belongs to a novel class of NMR active molecules (fluoroaryl-beta-D-galactopyranosides), which are highly responsive to the action of beta-galactosidase (beta-gal). OFPNPG has a single 19F peak (-55 ppm relative to aqueous sodium trifluoroacetate). Upon cleavage by beta-gal, the pH sensitive aglycone 2-fluoro-4-nitrophenol (OFPNP) is observed at a chemical shift of -59 to -61 ppm. The chemical shift response is sufficient to observe beta-gal activity using chemical shift imaging (CSI). 19F CSI studies of enzyme activity and lacZ gene expression in 9L-glioma and MCF7 breast cancer cells are presented, providing further evidence for the utility of OFPNPG as a gene-reporter molecule for future in vivo studies.
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PMID:Imaging beta-galactosidase activity using 19F chemical shift imaging of LacZ gene-reporter molecule 2-fluoro-4-nitrophenol-beta-D-galactopyranoside. 1691 13

Breast cancer is the most common cancer in women. Germline mutations in BRCA-1 and BRCA-2 significantly increase the risk of developing breast and ovarian cancers, and are also associated with an increased incidence of primary cancers at other sites. We report the case of a 46-year-old woman previously treated for ductal adenocarcinoma of the breast with BRCA-1 who subsequently was diagnosed with multicentric glioblastoma multiforme (GBM) in the right temporal and right occipital lobes. We briefly discuss the incidence of BRCA-1 mutations in breast cancer as well as other primary neoplasms and consider potential mechanisms shared in the pathogenesis of breast and glial tumors.
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PMID:Multicentric glioblastoma multiforme in a patient with BRCA-1 invasive breast cancer. 1695 68

Chromosomes of human malignant tumours display not only structural recombinations but also a wide variety of mostly non-random numerical aberrations. However, only little is known about the mechanisms leading to recurrent aneuploidies. We therefore investigated whether the malsegregation of specific chromosomes is due to a defect of the mitotic spindle apparatus. We analyzed mitoses of cell lines of six gliomas and of one breast carcinoma by combined immunohistochemistry and fluorescence in situ hybridization for non-disjunction of chromosomes 7, 8, 10, 12, 17, and 18 and observed three different phenomena. i) Five of six glioma cell lines showed a bipolar spindle but displayed a chromosome-specific malsegregation of all chromosomes studied with high but significantly different frequencies. Chromosomes 7 and 8 showed non-disjunction in about 75 and 50%, respectively. Although chromosomes 10, 12, 17, and 18 displayed equal separation during mitosis in 72, 86, 73, and 78%, respectively, a relevant percentage of an average of 24% of dividing cells showed even malsegregation of these chromosomes. ii) Only one of the glioma cell lines displayed multipolar spindles in one-third of the investigated cells resulting in non-specific aneuploidy. iii) The breast cancer cell line MCF7 displayed a bipolar spindle, but high frequencies of non-disjunction of all six investigated chromosomes but without preferential loss or gain of specific chromosomes indicating a different mechanism of chromosome malsegregation. In a small percentage of mitoses the chromatids of both homologous chromosomes were not separated mimicking the mechanism in the first meiotic division. This mechanism of double non-disjunction, not detectable by conventional cytogenetic analysis, procreates cell clones with genomic separation for particular chromosomes resulting in homozygosity for mutations which had been present heterozygously in the initial tumour cells.
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PMID:Different mechanisms of mitotic instability in cancer cell lines. 1708 76

Recombinant adeno-associated virus (AAV) is a promising non-pathogenic vector in the emerging field of gene therapy. For AAV serotype 2 (AAV-2) infection, experimental evidence points to an involvement of heparan sulphate proteoglycans (HSPG), but also to the existence of additional receptors. We investigated a potential role of the tetraspanin CD9 in AAV-2 infection of breast cancer cells mainly because it binds to the heparin-binding EGF-like growth factor, suggesting that it may also interact with a heparin-binding virus. Among breast cancer cell lines, expression of HSPG or potential AAV-2 (co)-receptors was not found to correlate with transduction efficiency. In complete accordance with the role of CD9, blocking with anti-CD9 antibodies resulted in drastically decreased AAV-2 transduction efficiencies in cell lines with low expression of HSPG. Furthermore, specific inhibition of CD9 expression with siRNA resulted in fewer transgene-positive cells, whereas overexpression of CD9 in the breast cancer cell line T47D as well as in BT8Ca and BT12Ca rat glioma cells (with low background expression of HSPG and CD9) increased the number of AAV-transduced cells. The minimal epitope recognized by antibody 72F6, which most efficiently blocked AAV-mediated transgene expression, was deduced from the specific binding to peptides immobilized on colour-encoded microspheres consisting of the amino acid sequence PKKDV located in the large extracellular loop of CD9. Our results clearly point to an involvement of CD9 in the attachment, uptake or processing of AAV-2 by target cells expressing low amounts of HSPG, which may help to define cell populations accessible in AAV-based therapeutic applications.
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PMID:CD9 promotes adeno-associated virus type 2 infection of mammary carcinoma cells with low cell surface expression of heparan sulphate proteoglycans. 1720 8

A promising clinical application of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PP IX) is fluorescence detection and photodynamic treatment of residual tumour tissue during surgical resection of high grade malignant glioma. U373 MG human glioblastoma cells were used as a model system to study the relation between intracellular location and photodynamic efficacy of 5-ALA-induced PP IX in more detail. Therefore, ultra-sensitive fluorescence microscopy, using either optical excitation of whole cells or selective excitation of the plasma membrane by an evanescent electromagnetic field, was combined with quantitative measurements of intracellular porphyrin amount and phototoxicity. Glioblastoma cells accumulated PP IX to a moderate extent as compared to T47D breast cancer cells (high accumulation) or OV2774 ovarian cancer cells (low accumulation). Although photodynamic inactivation of the different cell lines (decreasing in the order T47D > U373 MG > OV2774) seemed to be directly related to PP IX accumulation, examination of the data in more detail revealed that photodynamic efficacy per photosensitizer molecule (PE) was about two times higher in glioblastoma and ovarian cancer cells as compared to breast cancer cells. The different photodynamic efficacy of PP IX was related to the different intracellular location. In contrast to breast cancer cells where PP IX fluorescence was localized in small granules, PP IX fluorescence in glioblastoma cells and ovarian cancer cells originated mainly from cellular membranes. Thus, the intracellular location of PP IX in a predominantly lipophilic environment, characterized by a comparably high photostability (probed by photobleaching and photoproduct formation) and a lower degree of porphyrin aggregation (probed previously by fluorescence decay kinetics), seems to be the key factor for high photodynamic efficacy of 5-ALA-induced PP IX. In the case of OV2774 ovarian cancer cells, however, a low PP IX accumulation limited cell inactivation upon irradiation, whereas the results obtained for glioblastoma cells are encouraging to develop PDT to an additional therapeutic option for the treatment of tumour margins in patients who underwent fluorescence-guided resection of high grade malignant glioma after 5-ALA administration.
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PMID:Relation between intracellular location and photodynamic efficacy of 5-aminolevulinic acid-induced protoporphyrin IX in vitro. Comparison between human glioblastoma cells and other cancer cell lines. 1727 37

Wound-healing assay-guided fractionation of an EtOAc extract of the fungal strain Fusarium oxysporum EPH2RAA endophytic in Ephedra fasciculata afforded beauvericin (1), (-)-oxysporidinone (2), and two new N-methyl-2-pyridones, (-)-4,6'-anhydrooxysporidinone (3) and (-)-6-deoxyoxysporidinone (4). Beauvericin (1) inhibited migration of the metastatic prostate cancer (PC-3M) and breast cancer (MDA-MB-231) cells and showed antiangiogenic activity in HUVEC-2 cells at sublethal concentrations. Cytotoxicity-guided fractionation of an EtOAc extract of F. oxysporum strain CECIS occurring in Cylindropuntia echinocarpus afforded rhodolamprometrin (5), bikaverin (6), and the new natural product 6-deoxybikaverin (7). All compounds were evaluated for cytotoxicity in a panel of four sentinel cancer cell lines, NCI-H460 (non-small-cell lung), MIA Pa Ca-2 (pancreatic), MCF-7 (breast), and SF-268 (CNS glioma), and only beauvericin (1) and bikaverin (6) were active, with 1 and 6 showing selective toxicity toward NCI-H460 and MIA Pa Ca-2, respectively. Interestingly, 6-deoxybikaverin (7) was completely devoid of activity, suggesting the requirement of the C-6 hydroxy group of bikaverin for its cytotoxic activity.
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PMID:Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. 1728 29


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