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)

The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.
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PMID:The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells. 1277 71

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.
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PMID:The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors. 1295 97

The remarkable migratory and tumor-tropic capacities of neural stem cells (NSCs and/or neuroprogenitor cells) represent a potentially powerful approach to the treatment of invasive brain tumors, such as malignant gliomas. We have previously shown that whether implanted directly into or at distant sites from an experimental intracranial glioma, NSCs distributed efficiently throughout the main tumor mass and also tracked advancing tumor cells, while stably expressing a reporter transgene. As therapeutic proof-of-concept, NSCs genetically modified to produce the prodrug activating enzyme cytosine deaminase (CD), effected an 80% reduction in the resultant tumor mass, when tumor animals were treated with the systemic prodrug, 5-fluorocytosine. We now extend our findings of the tumor-tropic properties of NSCs (using a well-characterized, clonal NSC line C17.2), by investigating their capacity to target both intracranial and extracranial tumors, when administered into the peripheral vasculature. We furthermore demonstrate their capacity to target extracranial non-neural tumors such as prostate cancer and malignant melanoma. Well-characterized NSC lines (lacZ and/or CD-positive) were injected into the tail vein of adult nude mice with established experimental intracranial and/or subcutaneous flank tumors of neural and non-neural origin. The time course and distribution of NSCs within the tumor and internal organs was assessed in various models. Resulting data suggest that NSCs can localize to various tumor sites when injected via the peripheral vasculature, with little accumulation in normal tissues. Our findings suggest the novel use of intravascularly administered NSCs as an effective delivery vehicle to target and disseminate therapeutic agents to invasive tumors of neural and nonneural origin, both within and outside of the brain.
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PMID:Intravascular delivery of neural stem cell lines to target intracranial and extracranial tumors of neural and non-neural origin. 1467 Jan 28

Relatively few studies have examined glioma risk in relation to history of cancer in first-degree relatives. We sought to describe such risks in a large hospital-based case-control study. Histologically confirmed incident adult glioma cases (n = 489) were identified at three regional referral hospitals between June 1994 and August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant conditions were frequency-matched on age, sex, race/ethnicity, hospital, and proximity of residence to hospital. Participants received a personal interview, including questions regarding cancer in family members. Odds ratios (ORs) were calculated to estimate the risk of glioma associated with a history of cancer in a first-degree relative using conditional logistic regression and compared with standardized incidence ratios among relatives of cases versus relatives of controls. Among participants reporting a family history of a brain cancer or a brain tumor, risk of glioma was 1.6 [95% confidence interval (CI), 0.5-5.3; n = 5] and 3.0 (95% CI, 0.9-10.8; n = 7), respectively, in comparison with those without such family histories. Participants who had a family history of stomach (OR, 2.2; 95% CI, 1.0-4.6), colon (OR, 1.4; 95% CI, 0.9-2.2), or prostate cancer (OR, 2.1; 95% CI, 1.1-3.8) or Hodgkin disease (OR, 2.4; 95% CI, 0.9-6.3) had an increased glioma risk. OR estimates were similar to the ratios of standardized incidence ratios for cancer in relatives of cases versus controls. Shared environmental or genetic factors in families may influence glioma risk. Our findings suggest that individuals with a family history of specific cancers other than glioma may have an increased glioma risk.
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PMID:Cancer in first-degree relatives and risk of glioma in adults. 1469 35

Thalidomide, an oral agent with antiangiogenic and immunomodulatory properties, is being investigated extensively in the management of advanced cancer. Multiple studies with large numbers of patients have confirmed that this drug has significant activity in multiple myeloma. Some patients with myelofibrosis or myeodysplatic syndromes may reduce their need for transfusions after thalidomide treatment. The activity of thalidomide in solid tumors is less prominent. Studies in Kaposi's sarcoma, malignant melanoma, renal cell carcinoma and prostate cancer appear more promising especially when thalidomide is combined with biological agents or with chemotherapy. Limited activity was demonstrated in patients with glioma, while thalidomide appears to be inactive in patients with head and neck cancer, breast or ovarian cancer.
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PMID:Thalidomide in cancer medicine. 1527 53

Activation in transformed cells of normal stem cells' self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene-driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell-resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell-like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1-driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.
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PMID:Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. 1593 83

The involvement of alpha(v)beta3 and alpha(v)beta5 integrins in angiogenesis and the use of integrin antagonists as effective antiangiogenic agents are documented. Radiotherapy is an important therapy option for cancer. It has been shown that ionizing radiation exerts primarily antiangiogenic effects in tumors but has also proangiogenic effects as the reaction of the tumor to protect its own vasculature from radiation damage. Here, we show that combined treatment with S247, an Arg-Gly-Glu peptidomimetic antagonist of alpha(v)beta3 integrin, and external beam radiotherapy are beneficial in local tumor therapy. We found that radiation up-regulates alpha(v)beta3 expression in endothelial cells and consecutively phosphorylates Akt, which may provide a tumor escape mechanism from radiation injury mediated by integrin survival signaling. In the presence of S247, the radiation-induced Akt phosphorylation is strongly inhibited. Our studies on endothelial cell proliferation, migration, tube formation, apoptosis, and clonogenic survival show that the radiosensitivity of endothelial cells is enhanced by the concurrent administration of the integrin antagonist. The in vitro data are successfully translated into human glioma (U87), epidermoid (A431), and prostate cancer (PC3) xenograft models growing s.c. on BALB/c-nu/nu mice. In vivo, the combination of S247 treatment and fractionated radiotherapy (5 x 2.5 Gy) leads to enhanced antiangiogenic and antitumor effects compared with either monotherapies. These results underline the importance of alpha(v)beta3 integrin when tumors protect their microvasculature from radiation-induced damage. The data also indicate that the combination of integrin antagonists and radiotherapy represents a rational approach in local cancer therapy.
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PMID:Inhibition of alpha(v)beta3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy. 1614 31

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.
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PMID:A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer. 1635 94

Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial NMDAr staining was not seen. Of 18 benign prostatic hyperplasia (BPH) specimens, none had stromal NMDAr staining, but 2 had low and 1 had high epithelial NMDAr immunoreactivity. Moderate to high NMDAr immunostaining was observed in the stroma of 60 of 145 (41%) prostate cancer (PCa) specimens. Epithelial NMDAr staining was low in 26 (18%) and moderate to high in 36 (25%) of 145 PCa specimens. We have also examined the effects of the NMDAr antagonist memantine on the growth of ten human cancer cell lines: four prostate, two breast and four colon. The NMDAr antagonist memantine inhibited in-vitro growth of all ten cell lines, with half-maximal growth-inhibition at 5 to 20 microg/ml (23 to 92 microM) memantine. An NMDA agonist, L-cysteinesulfinic acid, stimulated cellular proliferation of all ten cell lines, with maximal growth-stimulation (30% to 75%, depending on the cell line) observed between doses of 33 to 66 microM. Our data provide evidence for the expression and activity of NMDAr in prostate cancer.
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PMID:N-methyl-D-aspartate receptor in human prostate cancer. 1636

Abnormalities of choline processing in cancer cells have been used as a basis for imaging of cancer with positron emission tomography and magnetic resonance spectroscopy. In this study, the transport mechanism for choline was investigated in cultured PC-3 prostate cancer cells. Furthermore, tritiated hemicholinium 3 (HC-3), a well-known inhibitor of choline transport, was studied as a prototypic molecular imaging probe in PC-3 cells and 9L glioma-bearing rats. [(3)H]Choline uptake by PC-3 cells was found to have both facilitative and nonfacilitative components. Facilitative transport was characterized by partial sodium dependence and intermediate affinity (K(M) = 9.7 +/- 0.8 microM). HC-3 inhibited choline with a K(I) of 10.5+/- 2.2 microM. Ouabain (1 mM) caused a 94% reduction in choline uptake. At physiologic choline concentration, phosphocholine was the rapid and predominant metabolic fate. The binding of [(3)H]HC-3 to PC-3 cells was rapid and specific (competitively blocked with unlabeled HC-3). Biodistribution of [(3)H]HC-3 in 9L glioma-bearing rats showed the ranking of uptake to be kidney > lung > tumor > liver > skeletal muscle congruent with blood > brain. In comparison with [(14)C]choline, [(3)H]HC-3 showed over twofold higher tumor uptake and favorable uptake ratios of tumor to blood, tumor to muscle, tumor to lung, and tumor to liver. The data demonstrate the quantitative importance of an intermediate-affinity, partially sodium-dependent choline transport system on choline processing in PC-3 cancer cells. The biodistribution properties of [(3)H]HC-3 in tumor-bearing rats encourage the development of molecular imaging probes based on choline transporter binding ligands.
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PMID:Choline transporter as a novel target for molecular imaging of cancer. 1715 Jan 62


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