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)

A review of misonidazole pharmacokinetics in 83 consecutive patients treated for tumours other than glioma has shown that among patients not receiving enzyme-inducing agents the plasma elimination half life is lower in patients taking steroids. Such a difference is not seen if patients already taking enzyme inducers are given steroids. Five further patients with carcinoma of the lung, treated with radiation over a period of 3 weeks, have been studied in greater detail. Misonidazole, in oral dose of 1 gm-2, was given in conjunction with the first and last radiotherapy fractions, and dexamethasone, in a divided daily dose of 8 mg, was given throughout the radiation treatment, commencing after the first treatment. Misonidazole pharmacokinetics were studied at each administration. Following the dexamethasone treatment period there was a 25% reduction in misonidazole plasma elimination half life, a 24% reduction in plasma AUC0-00, and a 38% increase in 24 h urinary excretion (all changes being statistically significant--P less than 0.005). No changes were observed in the plasma AUC0-24 and urinary excretion of the major metabolite desmethylmisonidazole. Glomerular filtration rates in one patient, before and after treatment with dexamethasone, remained unchanged. These results suggest that the effect of dexamethasone on misonidazole kinetics is not related to an enhancement of demethylation.
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PMID:The role of dexamethasone in the modification of misonidazole pharmacokinetics. 662 54

We have previously demonstrated that DNA of mouse fibroblasts transformed by 3-methylcholanthrene (3-MC) induced foci of transformed cells when applied to monolayer cultures of NIH3T3 cells, which indicates that at least a part of this phenotype is encoded in DNA sequences. However, our conclusions were confined to the effects of DNAs of 3-MC-transformed mouse fibroblasts on recipient NIH3T3 cells, also of mouse fibroblast origin. To elucidate this phenomenon further, we have prepared DNAs from a series of mouse and non-mouse tumour lines of non-fibroblastic origin and investigated whether tumour transforming genes can act across tissue and species barriers to transform NIH3T3 cells. We find that DNAs obtained from human, rabbit and mouse bladder carcinoma lines, a lung carcinoma line and rat neuroblastoma and mouse glioma lines, are able to induce transformation of NIH3T3 cells on transfection.
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PMID:Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. 720 18

N-Phosphonacetyl-L-aspartic acid (PALA) is new synthetic antimetabolite which inhibits de novo pyrimidine biosynthesis. Its significant activity against Lewis lung carcinoma, B16 melanoma, and glioma 26 suggested that it might be useful in the treatment of human solid tumors. Phase I trials revealed that dose-limiting toxicity included skin reactions, diarrhea, and stomatitis. Pharmacologic studies demonstrated rapid renal excretion of more than 70% of the unmetabolized drug in 24 h. Peak plasma levels correlated with dose of PALA administered. Partial responses to PALA were seen in one patient with melanoma, one with chondrosarcoma, and one with colon carcinoma. The potential for PALA's use in combination chemotherapy, particularly with 5-fluorouracil, is discussed.
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PMID:An overview of the clinical pharmacology of N-phosphonacetyl-L-aspartate (PALA), a new antimetabolite. 744 50

There is a renewed interest in positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) since the development of large field of view cameras and the capability of regional distribution of 18FDG. This method may help solve three types of problems in clinical oncology: tumor diagnosis and extension assessment, prediction of treatment response and follow-up (diagnosis of recurrences and complications). The aim of this paper is to review the literature in this field. This technique is mostly used for brain, lung, rectal and breast tumors as well as for sarcomas. It is possible to diagnose an anaplastic transformation of a low grade glioma since 18FDG uptake correlates with the histological grade. 18FDG plays another important role in the evaluation of the brain tumor response to treatment and of the secondary effects or sequelae of this treatment. This technique is also useful in breast carcinomas: diagnosis in the case of a dense breast, detection of lymph nodes or other metastases which could modify the strategy. One of the most established roles of 18FDG PET is the diagnosis of rectal tumor recurrences. Furthermore, future results will probably confirm its usefulness in lung carcinoma, for the diagnosis and for treatment evaluation. Lastly, it plays an important role in soft tissue sarcomas at all stages of diagnosis and treatment. The results of the literature still have to be completed. However, if the capability of predicting tumor response to treatment is confirmed, this method will play an important role in patient management and will modify treatment strategies.
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PMID:[Positron-emission tomography: role of 18F-fluorodeoxyglucose (18FDG) imaging in oncology]. 749 17

The reactivity of a mAb (M16) raised against a small cell lung carcinoma line is described. M16 identifies a surface antigen expressed on cells of neuroectodermal origin following activation, as well as neoplastic transformation. M16 antigen expression is increased on retinoblastoma and neuroblastoma cell lines upon 'in vitro' stimulation and it is induced 'in vivo' on glial cells activated following brain injury. Furthermore, glial tumors show levels of M16 molecule expression increasing with the degree of malignancy, and in a retinoblastoma cell line, the expression of M16 was inversely related to the level of HLA-Class I and N-CAM antigens. The M16 antigen may represent a marker of both activation and neoplastic progression for neuroectodermal cells.
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PMID:Biochemical characterization and membrane expression of an antigen shared by activated and neoplastic cells of neuroectodermal origin. 770 33

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental radioimmunotherapy. 849 64

Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume. Several growth factor receptor tyrosine kinases have been implicated in angiogenesis, including receptors for epidermal, fibroblast, and platelet-derived growth factors, as well as the receptors Flk-1/KDR, Flt-1 Tek/Tie-2, and Tie-1. Endothelial cells in the vessels of tumors express Flk-1/KDR, a receptor for vascular endothelial growth factor. Flk-1 was previously shown to play a role in angiogenesis and tumor formation of s.c. xenografts of C6 glioma cells using dominant-negative methodology. We now demonstrate that Flk-1 seems to be generally involved in the growth of a wide range of solid tumors, including mammary, ovarian, and lung carcinoma, as well as glioblastoma. Furthermore, survival times in rats bearing intracerebral tumors were prolonged using the same dominant-negative methodology. The involvement of Flk-1 in a variety of tumor types suggests an important role for Flk-1 in tumor angiogenesis.
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PMID:Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. 860 10

Two novel porphyrin-bisacridine conjugates (1 and 2) were designed as bifunctional antitumour agents to combine the DNA-binding character of the acridines and the photosensitizing capacity of porphyrin, and have been subjected to biophysical and biological evaluation. The interactions of the conjugates with calf thymus DNA were evaluated using viscometric, spectrophotometric and stopped-flow sodium dodecyl sulphate (SDS) sequestration methods. Both conjugates acted as bis-intercalators via the two acridine chromophores and displayed a longer residence time on DNA relative to the parent acridine ligand. Their biological activity in vitro was studied against the C6 rat glioma, MCF-7, GBM and A431 cell lines. Both conjugates were cytotoxic to all four cell lines. The ID50 (C6 glioma) was essentially the same as that of the parent acridine for one conjugate, but was increased 20-fold for the other, while both conjugates were approximately 10-fold more cytotoxic than the parent porphyrin component. The tissue distribution of the two conjugates was assessed in nude mice xenografted with a human small cell lung carcinoma (POVD). There were large differences in the tissue distribution of the two conjugates, with conjugate 2 localizing 8-fold more in the tumour than conjugate 1.
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PMID:Biophysical and biological evaluation of porphyrin-bisacridine conjugates. 866 8

In Asian countries, fast neutron therapy was first introduced at the National Institute of Radiological Sciences (NIRS), and followed by the Institute of Medical Science (IMS), Tokyo University, and Korea Cancer Center Hospital (KCCH). At NIRS, 2,129 patients were treated with d(30 MeV)+Be neutrons between 1975 and 1994. There were 274 patients referred for the treatment with P(50.5 MeV)+Be neutrons at KCCH during the period of 1986 through 1992. Unfortunately, fast neutron therapy performed at IMS was discontinued in 1991, where 458 patients had been treated with d(14 MeV)+Be neutrons since 1976. At NIRS, a vertical beam with multileaf collimator system was used for treatment of patients referred. The results showed that local control rates were 79% (19/24), 53% (14/26), and 89.3% (50/56) for carcinoma of the salivary gland, osteogenic sarcoma and carcinoma of the prostate, while complications for those were found to be 8.8, 8.3 and 17.8%, respectively. In the treatment of carcinoma of the lung, results were better for patients with adenocarcinoma than those with squamous cell carcinoma. Of 32 patients suffering from Pancoast tumor, 14 achieved local control, whereas 2 of 32 patients developed complications. On the other hand, salvage surgery was required in the treatment of malignant melanoma. In the treatment of malignant glioma, dose localization has to be improved in the target area to confirm local control. Experiences performed at KCCH have shown that, of 53 patients suffering from unresectable primary or recurrent rectal carcinomas, 28 achieved local control. It was concluded from the experiences with fast neutrons in Asian countries that adenocarcinomas as well as slowly growing tumors are indications for fast neutrons and that dose localization has to be improved in order to advance high LET radiation therapy. Clinical trials with 70 MeV protons started at NIRS in 1979, where the aim of study has been focused on treatment of choroidal melanoma, whereas, at Tsukuba University, 250 MeV protons have been used in the treatment of tumors deeply seated. Based on experiences of fast neutrons and protons, clinical trials with heavy ions initiated at NIRS in October 1994. Clinical studies with high LET radiations will be performed by using heavy ions in order to pursue indications of particle radiation therapy.
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PMID:Present status of fast neutron therapy in Asian countries. 894 58

Using the technique of DD-PCR (differential display-polymerase chain reaction) we isolated a novel gene (D2-2) that is overexpressed in glioblastoma multiforme tissue (GMT) as compared to normal brain tissue (NBT). D2-2 is also highly expressed in recurrent glioma, colon tumor metastatic to brain, breast tumors, prostate tumors and a prostate tumor cell line (LNCaP). Northern blot analysis showed that D2-2 is highly expressed in several tumor cell lines (MOLT lymphoblastic leukemia, SW480 colorectal adrenocarcinoma, A549 lung carcinoma, HL-60 promyelocytic leukemia, S3 HeLa cells, K-562 chronic myelogeneous leukemia and G361 melanoma) as compared to NBT. Additionally, D2-2 is very highly expressed in cell lines derived from glioblastomas, grade IV astrocytomas, normal human fetal astrocytes (NHFA) and glioma. D2-2 is moderately expressed in neuroblastoma, neuroectodermal and medulloblastoma tumor cell lines. D2-2 expression is localized to the frontal lobe, occipital lobe and the cerebellum in the normal brain. Normal tissues such as thyroid, stomach, adrenal cortex, small intestine and pancreas show high expression of D2-2. We also show that D2-2 is expressed 28-fold higher in fetal brain (20 weeks) than in adult brain. Sequence analysis of a 2.0-kb fragment for D2-2 shows no homology to known sequences in the data base.
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PMID:Isolation and characterization of a novel gene from human glioblastoma multiforme tumor tissue. 917 9


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