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)

B cells derived from peripheral-blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein-Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor-reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin-resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, 1F6, produced an antibody reactive with a cell-surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. 1F6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal-cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung-cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, 1 colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor-infiltrating B cells.
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PMID:Analysis of two human monoclonal antibodies against melanoma. 145 38

The Authors report the appearance of Central Nervous System lesions in three patients previously treated for ovarian carcinoma. In one case (Stage 1) the histological sample found a glioblastoma, in the others (Stage 3) the lesion was the metastases after systemic diffusion of the primary carcinoma. CNS metastases are rare and more frequently occur in advanced ovarian carcinoma. In patients at Stage 1, CNS isolated lesions may be primary tumors.
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PMID:[Cerebral lesions in patients with ovarian cancer]. 148 Mar 11

As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial.
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PMID:Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. 224 91

Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
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PMID:Interferon therapy in neoplastic diseases. 618 85

A serine proteinase inhibitor was purified from conditioned medium of the human glioblastoma cell line T98G. Analysis of its partial amino acid sequences indicated that this protein was identical to placental protein 5 (PP5), a placenta-derived glycoprotein with serine proteinase inhibitor activity, the amino acid sequence of which had been partially determined. cDNA cloning of PP5 demonstrated that it belonged to the Kunitz-type serine proteinase inhibitor family, having three putative Kunitz-type inhibitor domains, and that it was identical to a recently reported inhibitor, tissue factor pathway inhibitor-2 (TFPI-2) [Sprecher et al. (1994) Proc. Natl. Acad. Sci. USA 91, 3353-3357]. PP5/TFPI-2 transcripts were highly abundant in the full-term placenta and widely expressed in various adult human tissues, such as the liver, skeletal muscle, heart, kidney, and pancreas. Several ovarian carcinoma cells as well as T98G also contained significant amounts of the transcripts.
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PMID:cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: identification as placental protein 5 and tissue factor pathway inhibitor-2. 789 52

The structure of IL-13 receptor (IL-13R) is currently under investigation. Recently, two different human IL-13R chains, termed here IL-13R alpha and -alpha' have been cloned. We have examined various cancer and normal cell lines for the presence of mRNA for IL-13R alpha and alpha, as well as IL-4R p140 (termed beta chain) and IL-2R gamma c chains. In renal cell carcinoma, glioblastoma and ovarian carcinoma (IGROV-1) cell lines, both IL-13R alpha and alpha chains were expressed (type I IL-13R). In epidermoid, colon, ovarian adenocarcinoma (PA-1) and normal mouse fibroblast (COS7) cell lines, only IL-13R alpha' was expressed (type II IL-13R). In hematopoietic TF-1 and EBV-immortalized normal B cell lines only IL-13R alpha' but not alpha chain was expressed along with gamma c (type III or type IV IL-13R). IL-13R alpha' chain was faintly detected in human T cells. All cells expressed the IL-4Rp140 beta chain. These data provide a direct support for our model of IL-13R which consists of three different forms composed of different subunits.
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PMID:Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells. 929 58

The insulin-like growth factor I receptor (IGF-IR) plays an important role in cell transformation and in protection from apoptosis. Although the wild-type IGF-IR generally has an antiapoptotic effect, there are reports that its COOH terminus may actually generate a proapoptotic signal. Three different expression plasmids, all coding for the COOH-terminal sequences of the human IGF-IR, MyCF, CF, and MyKCF, were stably transfected into human ovarian carcinoma CaOV-3 cells. All three plasmids had no effect on monolayer growth but strongly inhibited colony formation in soft agar. Only one of the plasmids, MyCF, expressing the last 112 amino acids of the IGF-IR and carrying a myristylation signal, caused large-scale apoptosis of CaOV-3 cells in vivo and abrogation of tumorigenesis in nude mice. The plasmid expressing the MyCF sequence was also introduced into human glioblastoma T98G cells, where it decreased the clonogenicity of cells, caused a marked inhibition of colony formation in soft agar, and induced apoptosis in vivo. A double mutation at residues 1293 and 1294 of MyCF completely abrogated its inhibitory and proapoptotic activities. Neither the autophosphorylation of the IGF-IR nor the tyrosyl phosphorylation of IRS-1 was affected by the expression of the MyCF plasmid. These and other findings suggest that a stably expressed myristylated COOH terminus of the IGF-IR can induce apoptosis in human tumor cells in vivo and inhibit tumorigenesis in nude mice by a mechanism that avoids the protective effect of the IGF-IR.
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PMID:Inhibition of tumorigenesis and induction of apoptosis in human tumor cells by the stable expression of a myristylated COOH terminus of the insulin-like growth factor I receptor. 962 92

We report the distribution pattern of the target antigen of an IgG1 monoclonal antibody, Ki-OC III raised in BALB/C mice against solubilised ovarian adenocarcinoma, in normal tissue and in a collection of human tumour types. Special reference was made to benign and malignant ovarian tumours. The reactive antigen protein purified to homogeneity for a planned amino acid analysis showed three bands between 37-40 kDa. Immunohistochemical analysis revealed a specificity of 98% and a sensitivity of 77%. The tracer kinetics of the radiolabelled antibody were tested on a human ovarian carcinoma cell line in athymic mice. The results were compared to cell lines derived from breast and stomach carcinomas as well as to a human glioblastoma cell line. The results show the preferential uptake by ovarian cancer cells followed by breast cancer cell lines. In animal models, scintigraphic monitoring and direct measurement of the radio-labelled monoclonal antibody showed a preferential accumulation in tumours, in addition to high level signals in the liver, kidney, spleen and heart which were related to degradation, excretion and high circulation. The Ki-OC III reactive antigen could be a potential candidate for immunomonitoring of ovarian and possibly also of breast cancer, for in vivo tumour imaging as well as for histopathologic examinations.
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PMID:Characterization of a MAb to ovarian cancer and its possible diagnostic application. 1047 26

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 3 (BR-3). This gene is not expressed in normal human brain tissue samples but is expressed at high levels in human low-grade glioma tissue samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. Data base search analysis indicated that the BR-3 gene has strong homology to a genomic sequence present on chromosome 1 but no homology to expressed genes. Open reading frame analysis has indicated the presence of a 71 amino acids long protein sequence. A data base search for the protein sequence homology showed no similarity to known sequences. Expression analysis of BR-3 indicated that it is expressed at high level in six out of seven low-grade glioma samples analyzed. In addition low levels of BR-3 gene expression was observed in six out of seven anaplastic astrocytoma tissue samples analyzed. BR-3 expression was observed in four of eight glioblastoma samples analyzed. Expression analysis of normal human tissues indicated that it is expressed in kidney, skeletal muscle, lung, spleen and heart. No expression of the BR-3 gene was observed in brain, liver or testes tissue. To understand the role of the BR-3 gene in cancer in general, we studied its expression in other cancer cell lines. Except for lung and ovarian carcinoma, the BR-3 gene is expressed in breast carcinoma, colon adenocarcinoma, prostatic adenocarcinoma, and pancreatic adenocarcinoma tissue samples. On the basis of its sequence, unique expression pattern, we conclude that BR-3 gene product may play a critical role in the genesis of human gliomas tumors.
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PMID:Molecular characterization of a novel human brain tumor-associated gene BR-3. 1216 25

The granulin-epithelin precursor, progranulin, PC-cell-derived growth factor or acrogranin, is a high molecular weight secreted mitogen. It is abundantly expressed in rapidly cycling epithelial cells, in the immune system and in neurons, such as cerebellar Purkinje cells. Progranulin contributes to tumorigenesis in diverse cancers, including breast cancer, clear cell renal carcinoma, invasive ovarian carcinoma and glioblastoma. It regulates the rate of epithelial cell division in responsive epithelial cells, and confers an invasive phenotype on these cells. It is involved in the wound response. During embryogenesis, progranulin accelerates blastocyst formation, and is a growth factor for trophectodermal cells. In the neonate, progranulin, regulates the hormone-dependent virilization of the hypothalamus. It activates phosphorylation of Shc, and p44/42 MAPK (mitogen activated protein kinase) in the ERK (extracellular regulated kinase) signaling pathway; PI3K (phosophatidyl inositol-3-kinase), AKT/protein kinase B, and p70S6kinase in the phosophatidyl inositol-3-kinase pathway; and focal adhesion kinase in the adhesion/motility pathway. The signaling properties of progranulin are apparently similar to those of classic growth factors, but the functional properties of progranulin distinguish it from these molecules. Deleting the insulin-like growth factor I receptor from murine embryonic fibroblasts blocks proliferation in response to all classic growth factors, such as epidermal growth factor, or platelet-derived growth factor, whereas progranulin retains mitotic activity on these cells. The defined biological actions of progranulin probably represent a small fraction of its overall functions. Transcriptome analyses show that the progranulin gene is induced in numerous situations that vary from obesity to the transcriptional response of cells to antineoplastic drugs. Here, the biological roles of progranulin will be reviewed, with an emphasis on cancer and cell proliferation.
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PMID:Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. 1297 94


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