Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 herein the case of a 16-year-old boy diagnosed as having Turcot syndrome, otherwise known as glioma-polyposis syndrome. The patient was transferred from the Department of Neurosurgery where he was undergoing investigation of a brain tumor, to the Department of Medicine for investigation of gastrointestinal symptoms. The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. A subtotal colectomy with side-to-end ileoproctostomy and release of the invaginations was carried out. Multiple polyps were found in the colon, two of which, including a large polyp that obstructed the colonic lumen, were confirmed histologically to be adenocarcinoma. The remaining polyps were adenomas. A biopsy of the brain tumor confirmed a diagnosis of astrocytoma (WHO grade II). This case report describes the characteristic features of Turcot syndrome presented by this patient.
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PMID:Turcot syndrome with colonic obstruction and small intestinal invagination: report of a case. 1048 58

We investigated the ability of Fischer rat T9 glioblastoma cells transduced with cDNA genes for the secreted (s) or membrane-associated (m) isoform of M-CSF to elicit an antitumor response when implanted into syngeneic animals. Intracranial (i.c.) implantation of 1 x 10(5) T9 cells expressing mM-CSF (T9/mM-CSF) resulted in 80% tumor rejection. Electron microscopy of the T9/mM-CSF tumor site, 2-4 days postimplantation, showed marked infiltration by macrophages, many of which were in physical contact with the T9/mM-CSF cells. Animals that rejected T9/mM-CSF cells were resistant to i.c. rechallenge with T9 cells, but not syngeneic MadB106 breast adenocarcinoma cells, suggesting that T9-specific immunity can be generated within the brain via the endogenous APCs. Intracranial injection of parental T9, vector control (T9/LXSN), or T9 cells secreting M-CSF (T9/sM-CSF) was 100% fatal. Subcutaneous injection of 1 x 10(7) T9/sM-CSF, T9/LXSN, or parental T9 cells resulted in progressive tumors. In contrast, T9/mM-CSF cells injected s.c. were destroyed in 7-10 days and animals developed systemic immunity to parental T9 cells. Passive transfer of CD3+ T cells from the spleens of immune rats into naive recipients transferred T9 glioma-specific immunity. In vitro, splenocytes from T9/mM-CSF-immunized rats specifically proliferated in response to various syngeneic glioma stimulator cells. However, only marginal T cell-mediated cytotoxicity was observed by these splenocytes in a CTL assay against T9 target cells, regardless of restimulation with T9 cells. Subcutaneous immunization with viable T9/mM-CSF cells was effective in eradicating i.c. T9 tumors.
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PMID:Development of systemic immunity to glioblastoma multiforme using tumor cells genetically engineered to express the membrane-associated isoform of macrophage colony-stimulating factor. 1055 82

Extended schedules of oral etoposide have been evaluated in many types of advanced cancer. In addition to their use in the common solid tumours, extended schedules have been employed in Kaposi's sarcoma (both AIDS-related and endemic types), medulloblastoma, glioma, and hepatocellular carcinoma. Single agent activity was demonstrated in all of these tumour subtypes. For patients with carcinoma of unknown primary site, we have recently incorporated a 10-day oral etoposide schedule into a combination regimen that also includes paclitaxel and carboplatin. With this regimen we achieved a 47% response rate in a group of 53 evaluable patients, with a median survival of 13.4 months. Patients with adenocarcinoma and poorly differentiated carcinoma of unknown primary site had comparable response rates and survival. According to a large number of clinical trials and pharmacokinetic data, a daily oral etoposide dose of 50 mg/m2 consistently produces serum concentrations >1 mg/L for several hours each day. Lower doses fail to consistently produce this serum concentration, which is considered necessary for optimum tumoricidal activity. Optimal dose duration is 10 to 14 days, particularly when combination regimens are being employed. Oral etoposide has an established role as a single agent in patients with low grade non-Hodgkin's lymphoma, Kaposi's sarcoma, and testicular cancer (if residual carcinoma is resected after first-line treatment). The optimal use of extended-schedule etoposide in combination regimens is not defined but is being evaluated in a number of etoposide-sensitive malignancies.
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PMID:Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues. 1071 42

Exposure of cells to ionising radiation results in the activation of specific transcriptional control (CArG) elements within the early growth response 1 (Egr1) gene promoter, leading to increased gene expression. As part of a study investigating the potential use of these elements in radiation-controlled gene therapy vectors, we have incorporated their sequences into a synthetic gene promoter and assayed for the ability to induce expression of a downstream reporter gene following irradiation. In vector-transfected MCF-7 breast adenocarcinoma cells, the synthetic promoter was more effective than the wild-type Egr1 counterpart in up-regulating expression of the reporter gene after exposure to a single 5 Gy dose, and equally effective as the wild-type in U87-MG glioma cells. The level of gene expression achieved using the synthetic promoter was dependent on the inducing radiation dose for both U87-MG and MCF-7 cells, being maximal at 3 Gy and decreasing at 5 and 10 Gy. Furthermore, induction could be repeated by additional radiation treatments. The latter indicates that up-regulation should be additive during fractionated radiotherapy schedules. To demonstrate the potential clinical benefit of such an approach, the synthetic promoters were also shown to drive expression of the herpes simplex virus thymidine kinase gene, leading to enhanced cell killing in the presence of the prodrug ganciclovir (GCV) when compared with cells treated with radiation alone. Our results demonstrate that the synthetic promoter is responsive to low doses of ionising radiation and therefore isolated CArG elements function as radiation-mediated transcriptional enhancers outside their normal sequence context. The continued development and optimisation of such radiation-responsive synthetic promoters is expected to make a valuable contribution to the development of future radiation-responsive vectors for cancer gene therapy.
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PMID:Development of synthetic promoters for radiation-mediated gene therapy. 1108 80

The RNase-like onconase, isolated from amphibian oocytes, showed increases in median tumor pO2 in solid tumors (1). This led us to consider if onconase could decrease cellular O2 consumption (QO2) on 9L rat glioma as well as DU145 human prostate adenocarcinoma cells. Using a Clark-type electrode chamber, we observed that onconase significantly inhibited QO2 in both tumors we tested. Since onconase-induced reduction in QO2 could lead to increases in radiation sensitivity, due to the diffusion of O2 to previously hypoxic tumor cells, we used androgen-insensitive DU145 cells to study onconase-induced changes in radiation sensitivity in vitro. Radiation sensitization was achieved with > 5 micrograms/ml of onconase, regardless of the p53 status of tumor cells. Data presented here suggested that onconase-induced enhancement in radiation sensitization in vitro of androgen-insensitive prostate cancer cells warranted further studies of radiation responses in vivo, prior to clinical settings for the advanced-stages of prostate cancer.
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PMID:Enhanced cellular radiation sensitivity of androgen-independent human prostate tumor cells by onconase. 1081 Mar 94

A recombinant MVMp of the fibrotropic strain of minute virus of mice (MVMp) expressing the chloramphenicol acetyltransferase reporter gene was used to infect a series of biologically relevant cultured cells, normal or tumor-derived, including normal melanocytes versus melanoma cells, normal mammary epithelial cells versus breast adenocarcinoma cells, and normal neurons or astrocytes versus glioma cells. As a reference cell system we used normal human fibroblasts versus the SV40-transformed fibroblast cell line NB324K. After infection, we observed good expression of the reporter gene in the different tumor cell types, but only poor expression if any in the corresponding normal cells. We also constructed a recombinant MVMp expressing the green fluorescent protein reporter gene and assessed by flow cytometry the efficiency of gene transduction into the different target cells. At a multiplicity of infection of 30, we observed substantial transduction of the gene into most of the tumor cell types tested, but only marginal transduction into normal cells under the same experimental conditions. Finally, we demonstrated that a recombinant MVMp expressing the herpes simplex virus thymidine kinase gene can, in vitro, cause efficient killing of most tumor cell types in the presence of ganciclovir, whilst affecting normal proliferating cells only marginally if at all. However, in the same experimental condition, breast tumor cells appeared to be resistant to GCV-mediated cytotoxicity, possibly because these cells are not susceptible to the bystander effect. Our data suggest that MVMp-based vectors could prove useful as selective vehicles for anticancer gene therapy, particularly for in vivo delivery of cytotoxic effector genes into tumor cells.
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PMID:Tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector. 1082 6

We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell line, with a retroviral expression vector containing the human IL-6 cDNA and investigated the effects of IL-6 secretion on glioma formation in the syngeneic Fischer rat. Two subclones producing high and low levels (35 and 3.5 ng/10(6) cells/48 h) of IL-6 were identified and were termed T9.F/IL6/hi and T9.F/IL6/lo, respectively. Subcutaneous (SC) injection of 1 x 10(6) parental T9.F cells resulted in 100% tumor formation and progression. When 1 x 10(6) IL-6 secreting T9.F cells were injected SC, a small palpable tumor formed which sometimes regressed. In this regard, no tumors were detected after 30 days in 76% (13/17) of animals injected with T9.F/IL6/hi cells, whereas only 10% (1/10) of the rats injected with T9.F/IL6/lo cells completely rejected their tumors within this time frame. The addition of an IL-6 neutralizing antibody to the T9.F/IL6/hi SC inoculum followed by an intratumoral injection of the IL-6 neutralizing antibody, seven days later, abrogated the anti-tumor effects. Animals that rejected the IL-6 secreting tumors were 100% protected from subsequent intracranial (IC) challenges with the parental T9.F glioma as well as the original T9 glioblastoma; partially protected from an IC challenge with the unrelated, syngeneic RT-2 glioma; but were not protected from an IC challenge with the syngeneic MadB106 adenocarcinoma. When 1 x 10(4) cells were injected in the brain of naive animals, survival time was significantly increased for those rats implanted with T9.F/IL6/hi cells, but not T9.F/IL6/lo cells, as compared to animals implanted with T9.F parental cells (p = 0.003). This study demonstrates that IL-6 secretion attenuates SC and IC glioma growth and SC rejection of IL-6 secreting T9.F cells induces long-term glioma immunity which is effective in the brain.
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PMID:Interleukin-6 transduction of a rat T9 glioma clone results in attenuated tumorigenicity and induces glioma immunity in Fischer F344 rats. 1084 91

Cathepsin B and in particular cell-surface and secreted cathepsin B has been implicated in the invasive and metastatic phenotype of numerous types of cancer. We describe here a method to easily survey cancer cell lines for cathepsin B activity using the highly selective substrate Z-Arg-Arg-AMC. Intact human U87 glioma cells hydrolyze Z-Arg-Arg-AMC with a Km of 460 microM at pH 7.0 and 37 degrees C. This is nearly the same as the Km of 430 microM obtained with purified cathepsin B assayed under the same conditions. The pericellular (i.e. both cell-surface and released) cathepsin B activity was inhibited by the cysteine protease inhibitors E-64, leupeptin, Mu-Np2-HphVS-2Np, Mu-Leu-HpHVSPh and the cathepsin B selective inhibitor Mu-Tyr(3,5 I2)-HphVSPh with IC50 values similar to those observed for the inhibition of purified human liver cathepsin B. Other human cancer cell lines with measurable pericellular cathepsin B activity included HT-1080 fibrosarcoma, MiaPaCa pancreatic, PC-3 prostate and HCT-116 colon. Cathepsin B activity correlated with protein levels of cathepsin B as determined by immunoblot analysis. Pericellular cathepsin B activity was also detected in the rat cell lines MatLyLu prostate and Mat B III adenocarcinoma and in the murine lines B16a melanoma and Lewis lung carcinoma. The ability to determine pericellular cathepsin B activity will be useful in selecting appropriate cell lines for use in vivo when analyzing the effects of inhibiting cathepsin B activity on tumor growth and metastasis.
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PMID:Fluorescent microplate assay for cancer cell-associated cathepsin B. 1086 20

Phage display techniques rely on nearly random oligonucleotide sequences inserted into the protein III filament binding protein of an Escherichia coli filamentous phage M13 to generate a library of phage that express more than 10(7) different peptides. Phage that expresses a sequence having high affinity for a specific molecule, cell, or tissue can then be isolated through selective binding and recovery. Selected phage cannot only be used as gene transfer vectors in themselves, but the small peptide epitopes can be sequenced and potentially recombined into the attachment proteins of viral vectors, or used by themselves to target other therapeutic agents and diagnostic imaging radiolabels. Most phage display selections are carried out against purified and/or fixed protein targets, raising concerns as to the relevance of the selected epitopes. We have selected phage from the CMTI library against viable U87-MG human malignant glioma cells using a derivation of biopanning. The library, which initially contained phage expressing 2x10(7) different epitope sequences, collapsed after four rounds of selection such that 42% of recovered clones expressed a consensus sequence. Selective binding to viable adherent U87-MG cells was subsequently demonstrated under physiologic conditions at 167% (+/-27%) unselected phage using a novel, viable enzyme-linked immunosorbent assay technique. In comparison, there was no difference in binding to control 9L rat gliosarcoma, PANC-1 human pancreatic adenocarcinoma, T98-MG human malignant glioma, or AST-4 human malignant glioma cells of selected compared to unselected phage. Using polymerase chain reaction, the epitope was recovered with flanking unique restriction sites for recombination into a herpes simplex virus type-1 vector. This study demonstrates and discusses optimized methodologies for using phage display to target viable cells.
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PMID:Isolation, characterization, and recovery of small peptide phage display epitopes selected against viable malignant glioma cells. 1149 72

Adoptive immunotherapy using OK-432-activated mononuclear cells (OK-MCs) offers cell-mediated and cytokine-mediated pathways for antitumor activity. The effectiveness of direct intratumoral administration of OK-MCs via a catheter/reservoir system was studied in patients with malignant brain tumors. Seventeen patients, 12 with malignant glioma, four with metastatic adenocarcinoma, and one with primary sarcoma of the brain, were treated by OK-MC therapy (1.0 to 11.2 x 10(7) cells/person) between June 1989 and April 1999. The OK-MC therapy was given to patients with tumors progressing despite previous cytoreductive surgery, radiation, or chemotherapy. Adverse effects seen after the therapy were fever in 10 patients, seizure in two patients, and hypotension in one patient. Evaluation by computed tomography or magnetic resonance imaging revealed that seven patients showed no change including three with minor response, and 10 showed progressive disease. Adoptive immunotherapy using OK-MC was safe and well tolerated, but the therapeutic potential is limited.
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PMID:Adoptive immunotherapy for malignant brain tumors using human peripheral blood mononuclear cells activated by the Streptococcal preparation OK-432. 1156 49


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