Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the B-chain of platelet-derived growth factor (PDGF) was analyzed in 29 human brain tumors (4 astrocytomas, 7 glioblastomas, 3 medulloblastomas, 3 oligodendrogliomas, 7 meningiomas, and others) using monoclonal antibody after digestion with alkaline phosphatase, and compared with proliferative activities measured by in vivo uptake of bromodeoxyuridine. Medulloblastomas contained the highest amounts of PDGF B-chain, some four to eight times more than that in control brain tissue. The most predominant PDGF molecule of the medulloblastoma was 17 kd. Astrocytomas, glioblastomas, oligodendrogliomas, and meningiomas contained predominantly 30 and/or 22-24 kd molecules. Glioblastoma and meningioma proliferative activities correlated closely to PDGF concentrations, with only a few exceptions. Tumors that contained a high level of PDGF B-chain showed high proliferative activity, while tumors with high proliferative activity did not always contain a high level of PDGF B-chain. Tumors that contain many PDGF B-chains may thus indicate malignancy.
 ...
PMID:Expression of the B-chain of platelet-derived growth factor and proliferative activity of human brain tumors. 768 50

Glioblastoma is the most malignant primary brain tumor. Inhibition of angiogenesis is one potential strategy for treating this fatal hypervascular tumor. AGM-1470 (also called TNP-470), a novel, potent, fungus-derived inhibitor of angiogenesis, was tested on the growth of human glioblastoma cells in culture and on the growth of the tumor in nude mice. In nude mice with subrenally implanted U-87 MG glioblastomas, AGM-1470 significantly inhibited tumor growth (P < 0.01), and in nude mice with intracranial U-87 MG glioblastomas, AGM-1470 prolonged survival. In addition to its expected action as an angiogenesis inhibitor, AGM-1470 also directly inhibited U-87 MG cells in culture at concentrations similar to those that inhibited endothelial cells. The combined inhibition of glioblastoma cell mitosis and of glioblastoma-induced neovascularization suggests that AGM-1470 should be considered for further investigation in the treatment of this fatal tumor.
 ...
PMID:AGM-1470 inhibits the growth of human glioblastoma cells in vitro and in vivo. 805 85

Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by flow cytometric analysis and 125I-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (KD = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers.
 ...
PMID:Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. 805 54

With only a few exceptions, the precursor cells representing the normal counterparts of human tumours are unknown. The comparative lack of information about the lineages involved in tissue development, and difficulties in growing many human tumors in a manner suitable for cellular biological analysis, together often make it difficult to study the differences between normal and tumor cells and to develop many of the model systems that would be useful in the study of human cancer. By applying techniques previously utilized to study glial progenitor cells, we have isolated a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conversation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible, and our results indicate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.
 ...
PMID:From rodent glial precursor cell to human glial neoplasia in the oligodendrocyte-type-2 astrocyte lineage. 858 59

The expression of connexin43, the primary gap-junction constituent of glial cells, was evaluated at the messenger RNA and protein levels in different grades of astrocytoma to investigate the relevance of gap junctions in herpes simplex virus-thymidine kinase (HSV-tk)-mediated gene therapy of brain tumors. Transduction of the retroviral-mediated HSV-tk gene into tumor cells with subsequent administration of ganciclovir has recently been used as an experimental therapeutic strategy for treatment of brain tumors. One aspect of this approach is the bystander effect, which augments the efficacy of this therapeutic approach. Glioblastoma cells with minimum levels of connexin43 protein were transfected with a connexin43 complementary DNA. These cells manifested a marked increase in the in vitro bystander effect, supporting the contention that the in vitro bystander effect is a consequence of metabolic cooperation between cells mediated by gap junctions. To assess relative levels of gap-junction protein expression in the relevant tumor type, we examined primary astrocytomas, primary astrocytoma cell cultures, and glioblastoma cell lines. Although most astrocytoma tumor samples expressed connexin43, they differed in the level of expression, with the greatest variation exhibited in high-grade astrocytomas. Primary glioblastoma cell cultures and established glioblastoma cell lines also displayed some variability in connexin43 levels. In aggregate, our results anticipate that glioblastomas will have a varied bystander effect during HSV-tk gene therapy depending on the level of connexin43 expression.
 ...
PMID:Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy. 862 59

Expression of CD44 and of specific splice-variants of CD44 has been causally related to metastatic behaviour in a variety of carcinomas and lymphomas. To elucidate whether, in principle, similar splice-variants could be involved in glioma cell invasion we examined the expression of CD44 and its splice-variants in a series of 38 primary human brain tumors (28 astrocytomas, WHO grade I-III and 10 glioblastomas, WHO grade IV) and in cell lines derived from 9 glioblastomas. All brain tumors examined showed strong immunoreactivity for an N-terminal epitope present on all CD44 isoforms known. Using a polyclonal antiserum raised against the complete sequence encoded by variant exons v3 to v10, CD44 splice-variants could be detected irrespective of the grade of malignancy in many of the tumor samples at a low level and often restricted to only a few clustered tumor cells. Thus, the N-terminal epitope probably indicates the presence of the smallest and most ubiquitous isoform CD44s. Interestingly, all glioblastomas expressed CD44 variants whereas expression in astrocytomas WHO grade I, II, and III could only be detected in about half of the tumor samples. Using reverse transcriptase-PCR we were able to detect different CD44 splice-variants in the glioblastoma cell lines and in cultured primary astrocytic cells. Glioblastoma cells analyzed by flow cytometry showed the expected binding capacity for hyaluronic acid which could be increased twofold after pretreatment with hyaluronidase. The results presented show that there is low expression of CD44 variants in human tumors of astrocytic origin. Expression of CD44 and its splice-variants could contribute to the migration capacity of neoplastic astrocytes, and may be considered as a target for new diagnostic and therapeutic approaches in the clinical management of brain tumors.
 ...
PMID:Expression of variant CD44 epitopes in human astrocytic brain tumors. 875 Jan 82

Glioblastoma cells secrete transforming growth factor-beta (TGF-beta), which has a variety of immunosuppressive properties. We investigated the effect of irradiation TGF-beta secretion by malignant glioma cells. Three malignant glioma cell lines (T98G, A172, KG-1-C) were cultured and irradiated using 10 and 50 Gy Linac radiation. After further culture for 36 hours in serum-free culture medium, the supernatants were collected. The TGF-beta activity in the culture supernatants was determined using a specific bioassay. The levels of the active form and total TGF-beta in the supernatants from irradiated malignant glioma cells decreased compared to those from un-irradiated cells. However, since irradiation inhibited the growth of tumor cells, the amount of TGF-beta secretion per cell in irradiated cells tended to increase after irradiation. These results suggest that malignant glioma cells can still secrete TGF-beta and activate latent TGF-beta even after large dose irradiation, despite the inhibition of tumor growth.
 ...
PMID:Effect of irradiation on transforming growth factor-beta secretion by malignant glioma cells. 919 90

In order to study the clinicopathological features, histogenesis and prognosis, 12 cases of gliosarcoma were reported representing 0.4% of a series of 2743 patients undergoing biopsy for CNS tumors. All the tumors originated from the cerebral hemispheres with a predilection for the temporal lobes. Half of the cases show more firm consistency and are rather well demarcated from brain tissue. Clinically, they are sometimes mistaken for meningiomas. Of the 10 patients with follow-up, 9 have died. The mean survival period after operation was 8 months, 1 cases is still alive and well for 3.2 years. There were some cases in which the origin of spindle cell populations could not be determined by H & E staining. Glioblastoma and malignant fibrous histiocytoma (MFH) element of the tumor was confirmed by electron microscopical examination and immunohistochemical stains for GFAP, Mac 387, VIM, FV III RA, etc. Osteosarcoma component in the tumor was detected in one case. It was accepted that MFH arose from the primitive uncommited mesenchyme.
 ...
PMID:[A clinical and pathological study of gliosarcoma]. 927 62

Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential.
 ...
PMID:Molecular genetic analysis of giant cell glioblastomas. 928 34

The abilities of growth factors to cause normal cells to express the properties associated with transformed cells is discussed in specific reference to the oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. In the O-2A lineage, it has been possible to use growth factors and other defined molecules to induce or promote in normal cells all of the main properties of tumor cells, these being continued cell division in the absence of differentiation, more subtle modulations of self-renewal probabilities, promotion of cell migration and inhibition of programmed cell death. In addition to our studies on primary cells, our application to the growth of human tumor specimens of techniques utilized to study primary glial progenitor cells has allowed us to isolate a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conservation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible. Our results thus demonstrate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. Our analyses further indicate that at least two distinct glial lineages can generate glioblastomas. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.
 ...
PMID:Growth factors, glia and gliomas. 944 20


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