Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were found to express p185HER2 at low to undetectable levels by Western blot technique. In contrast, 13 lung cancer cell lines expressed p185HER2, and eight of these 13 expressed p185HER2 at levels at least 2-fold higher than that found in normal bronchiole epithelial cells or type II pneumocytes. Genomic Southern analysis showed that amplification of the HER2 gene was present in only one of the eight cell lines that expressed p185HER2 at these higher levels. Increased levels of steady-state HER2 mRNA occurred in the remaining seven cell lines. We conclude that in human non-small cell lung carcinoma cell lines the most common mechanism resulting in increased p185HER2 expression is due to mechanisms that increase HER2 mRNA levels, with HER2 gene amplification occurring less commonly.
Am J Respir Cell Mol Biol 1992 Apr
PMID:Mechanisms of p185HER2 expression in human non-small cell lung cancer cell lines. 131 50

P68 is a protein kinase expressed by eukaryotic cells, which is inducible by alpha interferon, and is believed to be an important factor in the regulation of viral and cellular protein synthesis. We have previously reported on a monoclonal antibody, TJ4C4, which is able to specifically detect p68 in formalin-fixed, paraffin-embedded tissue. Because of its important role in regulating cellular protein synthesis, we hypothesized that p68 expression would vary among lung neoplasms with level of differentiation and degree of biosynthetic activity. A total of 246 untreated primary pulmonary and pleural neoplasms were studied. The frequency and relative intensity of p68 expression was determined by light microscopic evaluation of ABC immunoperoxidase stained specimens. All categories of tumors studied demonstrated a spectrum of p68 expression. Expression of p68 correlated well with degree of differentiation in squamous cell carcinomas (SQCC) and acinar adenocarcinomas (AAC). Papillary adenocarcinoma (PAC) and bronchioalveolar carcinoma (BAC) expressed low levels of p68, despite their well differentiated appearance. Expression of the antigen in large cell carcinoma (LCC) was higher than that seen in either poorly differentiated AAC or SQCC. Neuroendocrine tumors generally showed low levels of p68 expression with the intermediate variant of small cell carcinoma expressing higher levels of p68 than the classic "oat cell" form (SCC). Carcinoid tumors expressed higher levels of p68 than did atypical carcinoid tumors. Mesotheliomas showed weak expression of p68, limited primarily to areas of glandular differentiation in the epithelioid form.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Expression of the protein kinase p-68 recognized by the monoclonal antibody TJ4C4 in human lung neoplasms. 135 15

Interstitial deletions of the short arm of chromosome 9 are associated with glioma, acute lymphoblastic leukemia, melanoma, mesothelioma, lung cancer, and bladder cancer. The distal breakpoints of the deletions (in relation to the centromere) in 14 glioma and leukemia cell lines have been mapped within the 400 kb IFN gene cluster located at band 9p21. To obtain information about the mechanism of these deletions, we have isolated and analyzed the nucleotide sequences at the breakpoint junctions in two glioma-derived cell lines. The A1235 cell line has a complex rearrangement of chromosome 9, including a deletion and an inversion that results in two breakpoint junctions. Both breakpoints of the distal inversion junction occurred within AT-rich regions. In the A172 cell line, a tandem heptamer repeat was found on either side of the deletion breakpoint junction. The distal breakpoint occurred 5' of IFNA2; the 256 bp sequenced from the proximal side of the breakpoint revealed 95% homology to long interspersed nuclear elements. One- and two-base-pair overlaps were observed at these junctions. The possible role of sequence overlaps, and repetitive sequences, in the rearrangement is discussed.
Mol Cell Biol 1994 Nov
PMID:Breakpoint junctions of chromosome 9p deletions in two human glioma cell lines. 752 63

Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another mesothelioma cell line and a lung cancer cell line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment approach appears safe, with limited dissemination of virus using a sensitive RT-PCR detection system. These studies further characterize the use of adenoviral transfer of the HSVtk gene to treat experimental mesothelioma and suggest that clinical trials using this approach may be feasible.
Am J Respir Cell Mol Biol 1995 Jul
PMID:Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer. 759 39

The relationship between occupational or environmental exposure to asbestos and the development of mesothelioma, typically after prolonged latency, has been accepted as one of cause and effect. Most studies have concluded that asbestos is not mutagenic to mammalian cells in vitro. We have studied the potential of crocidolite asbestos to induce mutations in a stable mesothelioma cell line, using a mutation assay that measures mutation at the autosomal HLA-A locus and permits clonal growth of mutant cells. The mesothelioma cell line chosen is more akin to the in vivo target cells of asbestos than human peripheral blood lymphocytes used in previous studies. Exposure of mesothelioma cells in culture to both 200 micrograms/ml and 50 micrograms/ml crocidolite for 72 hr did not result in a statistically significant difference in the mutation frequency (MF) in the HLA-A assay when compared to the spontaneous MF in these cells. Mutations in the mesothelioma cells were classified according to their molecular basis. Notwithstanding the lack of statistically significant change in overall MF, molecular analysis of mutants obtained following exposure of mesothelioma cells to crocidolite demonstrated a statistically significant increase in the class of mutations arising from loss of heterozygosity (LOH) events involving the selection locus (HLA-A) and more distal loci. Mutations following exposure to 200 micrograms/ml and 50 micrograms/ml crocidolite showed a greater frequency of LOH than did spontaneous mutants (P < 0.01 and P < 0.001, respectively). These results correlate with those obtained in an earlier study using lymphocytes. The mesothelioma cell-based assay may be useful in detecting the mutagenicity of other asbestiform fibers and man-made fibers.
Environ Mol Mutagen 1995
PMID:Loss of heterozygosity in asbestos-induced mutations in a human mesothelioma cell line. 764 9

Malignant mesothelioma in humans is a rare disease, but it has recently received much public attention and concern because of its strong relationship to exposure to asbestos. We have found overexpression of the gene for platelet-derived growth factor (PDGF)-beta in several mesothelioma xenografts in nude mice. Because some mesothelioma cell lines such as VAMT-1 overexpress PDGF-beta and PDGF-beta receptors, it was considered that an autocrine loop involving PDGF-beta and its receptor may contribute to the malignant phenotype of these cells. To investigate this possibility we have developed a hammerhead ribozyme against PDGF-beta mRNA. This c-sis ribozyme was able to cleave an artificial PDGF-beta RNA substrate in a cell-free system. Transduction of this ribozyme, with the aid of a constitutive expression vector, in the VAMT-1 cell line led to a decrease in the PDGF-beta mRNA level. The ribozyme expressed in these cells was functional in cleaving the artificial RNA substrate in vitro. Ribonuclease protection assays using the ribozyme and whole PDGF-beta mRNA showed that this ribozyme was capable of cleaving the whole mRNA in vivo. Transfectant clones containing the wild-type ribozyme showed decreased cell growth, in parallel with the decreases in PDGF-beta expression. The disabled ribozyme was inactive in the cleavage reaction in vitro and in decreasing the cell growth rate in vivo. Our data indicate that in some mesothelioma cells the PDGF-beta autocrine loop may be functional and transduction of the PDGF-beta ribozyme leads to a significant reduction of cell growth. The c-sis ribozyme may be applicable in the treatment of patients with malignant mesothelioma.
Mol Pharmacol 1994 Sep
PMID:Modulation of platelet-derived growth factor-beta mRNA expression and cell growth in a human mesothelioma cell line by a hammerhead ribozyme. 793 23

To study mechanisms of cell proliferation by asbestos and nonasbestos fibers, we examined the effects of these agents on the mRNA levels of c-fos and c-jun and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells, the progenitor cells of bronchogenic carcinoma and mesothelioma, respectively. In comparison with crocidolite asbestos, increases in c-jun mRNA were less striking in HTE cells after exposure to man-made vitreous fiber-10 (MMVF-10) or refractory ceramic fiber-1 (RCF-1). No c-fos mRNA was detected in HTE cells after exposure to particulates, but exposure of HTE cells to H2O2 caused striking increases in c-fos and c-jun, which preceded increases in ODC mRNA. Increases in ODC mRNA were also observed in HTE cells after exposure to nonasbestos fibers, whereas only crocidolite asbestos caused elevations in ODC mRNA in RPM cells. In RPM cells, crocidolite and chrysotile asbestos caused increases in mRNA levels of both c-fos and c-jun. No increases in proto-oncogene induction were observed using MMVF-10 or RCF-1 at nontoxic concentrations (< or = 5 micrograms/cm2 dish). Moreover, erionite, a fiber extremely potent in the causation of mesothelioma in humans, caused more dramatic elevations in c-fos and c-jun. Nonfibrous particles (riebeckite, polystyrene beads) did not alter proto-oncogene expression in these cell types, suggesting that the fibrous geometry of particulates is critical in the induction of c-fos and c-jun.
Am J Respir Cell Mol Biol 1994 Nov
PMID:Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers. 794 82

Systemic amyloidosis of the amyloid A (AA) type, is occasionally associated with various neoplasms, but the cause is still unclear. We obtained interleukin 6 (IL-6)-producing cells designated YO from a primary culture of a malignant peritoneal mesothelioma of epithelial type obtained from a 62-year-old woman. Post mortem examination revealed that the patient had systemic amyloidosis of the AA type. The supernatant media of YO cells, as well as recombinant human IL-6, successfully induced nonneoplastic liver cells to produce serum AA (SAA). Our data suggest that IL-6 produced by the tumor cells may have played an important role in the paraneoplastic syndrome of AA amyloidosis in this patient.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Interleukin 6-producing malignant mesothelioma. 814 57

Overexpression of platelet-derived growth factor (PDGF)-A as well as PDGF-B chain mRNA has previously been reported in human mesothelioma cell lines. In this report, it has been established that the A but not the B chain protein is expressed at detectable levels in cell lysates and conditioned medium from these cell lines. In order to investigate the effect of overexpression of PDGF-A chain in a human mesothelial cell model system, a retroviral vector containing a human PDGF-A chain cDNA insert under the control of the Moloney murine leukemia virus (MoMLV) promoter was inserted into the SV-40 T-antigen immortalized human mesothelial cell line MeT-5A. Selected cells showed overexpression of PDGF-A chain relative to MeT-5A and induced tumors in athymic nude mice. PDGF-A chain overexpression was also found in the tumor specimens excised from the mice. PDGF-A mRNA and protein were expressed at a higher level in the tumor explant cell lines, suggesting a correlation of tumorigenicity with A chain production.
Am J Respir Cell Mol Biol 1993 Feb
PMID:Tumorigenic conversion of human mesothelial cells as a consequence of platelet-derived growth factor-A chain overexpression. 842 11

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1 beta, 2 and 6, tumor necrosis factor-alpha (TNF alpha) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16+ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16+ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Med (Berl) 1995 Aug
PMID:Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC. 852 43


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