Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells.
 ...
PMID:Detection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization. 786 8

Topoisomerase I (topo I) gene expression and cell sensitivity to camptothecin were investigated in seven human cancer cell lines not selected in vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2780 and IGROV-1), a cervix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a glioblastoma (GBM) and two different clones of a malignant melanoma (665/2/60 and 665/2/21). Topo I gene expression was evaluated by Northern blotting analysis and cell sensitivity to camptothecin was determined using the colony-forming assay after a 1 h exposure to the drug. A wide range of drug sensitivity levels was found among the examined cell lines. Cell doubling times and distribution in cell cycle phases were not correlated with camptothecin cytotoxicity. In particular, the percent of untreated cells in S phase was not predictive of the drug sensitivity. No correlation was found between level of topo I gene expression and cell response to camptothecin. These results indicate that the level of topo I expression is not the only critical determinant of cell sensitivity to camptothecin in unselected human cancer cell lines. Therefore, topo I gene expression may not be a useful predictive parameter of tumor response.
 ...
PMID:Topoisomerase I gene expression and cell sensitivity to camptothecin in human cell lines of different tumor types. 788 2

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
 ...
PMID:[Interferon-alpha, beta, gamma]. 799 28

Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified. T1 relaxation times for the most prominent compounds are presented. T1 values of lactate ranged between 450 ms and 850 ms. The intensity of the lactate signal revealed differences between individual spectra, but exhibited no correlation between different tumor specimens or degree of malignancy. It was shown that the lactate signal at 1.3 ppm is covered by peaks arising from threonine and fatty acids. The choline signal level varied among spectra of different tumors, among tumors with similar degree of malignancy, and within the same tumor. Further preliminary differences due to aspartate, inositol and glutamine/glutamate were found in 1D and 2D COSY spectra between normal glial cells as well as different tumors. These results indicate that some differences observed in in vivo spectra may be attributable to secondary macroscopic structural changes (hypoxia, necrosis) and not to tumor inherent characteristics. Further correlation between in vivo and in vitro spectroscopy is therefore required.
 ...
PMID:High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells. 808 Jul 12

The in vitro cytotoxicity, protein binding, partitioning of platinum from whole blood into erythrocytes, its exchange back into plasma, and the in vitro biotransformation in plasma were studied for the new nonnephrotoxic platinum analogue oxaliplatin. The cytotoxicity studies were carried out against a panel of human tumor cell lines derived from carcinomas of the ovary (A2780, A2780/cp), bladder (TCCSUP, RT4), colon (HT-29), melanoma (SKMEL-2, HTB144), and glioma (U373MG and U87MG). The relative potency of the five platinum complexes was oxaliplatin = tetraplatin > cisplatin > iproplatin > carboplatin. Oxaliplatin was active against HT-29 and only minimally cross-resistant with cisplatin against A2780/cp. Both bladder carcinoma cell lines, both melanoma cell lines, and one of the two glioblastoma cell lines were resistant to both oxaliplatin and tetraplatin. The cytotoxicity profiles of the drug pairs oxaliplatin-tetraplatin and cisplatin-carboplatin showed statistically significant correlation by the Spearman rank correlation test. Oxaliplatin was similar to cisplatin and tetraplatin in protein binding; 85-88% of all platinum from oxaliplatin (5, 10, or 20 micrograms/ml) was bound to plasma proteins within the first 5 h with an average half-life of 1.71 +/- 0.06 h. When oxaliplatin was incubated in whole blood (5, 10, and 20 micrograms/ml), the erythrocytes took up 37.1 +/- 2.1% of the total platinum in 2 h (maximum uptake) which was not exchangeable into plasma. Thus the erythrocyte-bound fraction does not serve as a reservoir of drug. In plasma, oxaliplatin was unchanged at 0.5 h, but at 1 h, 30% of the total platinum in plasma was in a peak which had identical retention to that of (trans-1,2-diaminocyclohexane)dichloroplatinum(II), the major biotransformation product of tetraplatin. At 2 h, (trans-1,2-diaminocyclohexane)dichloroplatinum(II) and three other platinum-containing peaks were detected but no unchanged oxaliplatin. All the platinum eluted in a single peak near the solvent front at 4 h. The marked similarity in cytotoxicity between oxaliplatin and tetraplatin may be due to the formation of (trans-1,2-diaminocyclohexane)dichloroplatinum(II) in tissue culture media.
 ...
PMID:In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. 826 11

Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors. 832 32

Neuroectodermal tumours express hormones which are post-translationally processed and inactivated by the action of specific proteases and peptidases. The data reported here show the presence of a novel thermolysin-like metallo-endopeptidase activity in several human cell lines. The soluble fractions of neuroblastoma, melanoma and a glioblastoma tumour cell lines are able, with different degrees, to cleave the Ser12-Phe13 bond of a DVDERDVRGFAS decreases FLNH2 substrate. The inhibition pattern suggests a metallo-endopeptidase thermolysin-like character, with the involvement of thiol group(s), clearly distinct from neutral endopeptidase (NEP; EC 3.4.24.11). This metallo-endopeptidase activity is down regulated during retinoic acid(RA)-induced neuronal differentiation in the RA-sensitive SK-N-BE(2) cells but not in the RA-resistant BE(2)-M17 cells, suggesting that the down regulation is related to neuronal differentiation and not a direct effect of RA on the enzymatic activity.
 ...
PMID:Modulation of a novel thermolysin-like metallo-endopeptidase activity during retinoic acid-induced differentiation of human neuroectodermal tumor cell lines. 838 87

Neutron capture therapy (NCT) is a form of radiation therapy using nuclides having a high propensity for capturing thermal neutrons and reacting with a prompt nuclear reaction (i.e. disintegration). If these nuclides are introduced selectively into tumor cells it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. The principles of this modality were described in 1936. First clinical trials in the USA from 1951 to 1961 using 10B resulted in failure. Since 1968 patients suffering from glioblastoma have been successfully treated in Japan by NCT with 10B and since 1987 another Japanese group has treated melanoma using NCT. The Japanese experiences and recent advances in the evaluation of tumor-affinitive boron-containing drugs have spurred interest in NCT. This article presents some basic physical notions and a historic overview of NCT that emphasizes the well documented early trials as well as some recent developments. Problems which occurred in the past now demand special efforts for a better understanding of the effects of NCT before starting new clinical trials in the next few years.
 ...
PMID:Principles and history of neutron capture therapy. 843 33

An IgM human monoclonal antibody (HuMAb) SK1 was generated from mesenteric nodal lymphocytes of a colon cancer patient that were fused with a human B-lymphoblastoid cell line SHFP-1. The reactivities of HuMAb SK1 to various human cell lines were screened by cell enzyme linked immunosorbent assay and immunocytochemical staining. The HuMAb SK1 reacted strongly with all 11 human carcinoma cell lines that were tested and had no detectable binding with noncarcinoma cell lines of the following origins: fibroblast; fetal lung; melanoma; soft tissue sarcoma; neuroblastoma; and glioblastoma. Carcinoma preferred reactivity of HuMAb SK1 was further confirmed by immunoperoxidase staining of a large number of frozen tissues, both malignant and benign. The antigen SK1 (AgSK1) in human carcinoma detected by immunoperoxidase staining was also identified biochemically as a sialoglycoprotein that migrated at M(r) 42,000 with an isoelectric point (pI) of approximately 5.9. A preferential staining by HuMAb SK1 was seen among colorectal, gastric, pancreatic, and lung cancers. Competitive inhibition study in solid-phase immunoassay suggested that the HuMAb SK1 did not cross-react with other antibodies specific for CEA, CA 19-9, and TAG 72. The AgSK1 appears to be a novel carcinoma associated antigen which may be a useful tumor marker in cancer diagnosis and treatment.
 ...
PMID:AgSK1, a novel carcinoma associated antigen. 843 57

Radionuclides are applied in oncology for diagnosis and therapy. The former demands gamma--emitting radionuclides for labeling specific substrates for localizing malignant tissue and for analyzing tumor metabolism in vivo. Here, positron emission tomography (PET) may register in vivo the metabolism, for example, of glucose, amino acids, and receptors and of potentially useful cytotoxic agents. The advantage of the positron emitting radionuclides of carbon, nitrogen and fluorine is the labeling of substrates without changing substrate specificity within the metabolic reaction chain; also, substrate concentration in situ may be quantified. With regard to therapy radionuclides that emit beta- and alpha-particles or decay by electron capture with the Auger effect, are administered in ionic form or with tumor seeking substrates. Examples are radioiodine for treating thyroid malignancy and radiophosphorus for myeloproliferative diseases. Organically bound radionuclides are given as labeled ligands for specific receptors, such as meta-iodo-benzylguanidine (MIBG) for treating the catecholamine producing tumors phaeochromocytoma and neuroblastoma and labeled monoclonal antibodies for tumors specific receptors. Highly localized energy depositions come from Auger emitters such as 125I and by the neutron capture therapy, where boron-10 in the tumor cell is exposed to thermal neutrons for initiating the B10 (n; alpha) Li7 reaction, especially for treating neuro- and glioblastoma and melanoma. Endogenous radiotherapy with radionuclides rely on the success of delivering a proper amount of energy into individual tumor cells with optimal protection of normal tissue. The inevitable heterogeneity of energy deposition events from such approaches demands careful dosimetric assessment for which the classical methods of dosimetry for percutaneous radiotherapy are not applicable.
 ...
PMID:Contributions of nuclear medicine to the therapy of malignant tumors. 844 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>