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

A putative tumor-suppressor gene (wt1) located at chromosome 11p13 and involved in Wilms' tumor development has recently been identified as a zinc finger polypeptide-encoding gene. The purpose of this study was to characterize the protein encoded by the human wt1 gene. The region spanning the entire zinc finger domain was amplified by polymerase chain reaction (PCR) and subcloned in the pATH 3 expression vector. Polyclonal antibodies against the fused TrpE-WT protein were raised. These antibodies immunoprecipitated a 49- to 51-kDa protein from hematopoietic tumor cells labeled in vivo with [35S]methionine. Subcellular fractionation and immunohistochemistry followed by confocal microscopy indicated that the Wilms' tumor gene product (WT1) is mainly localized within the nucleus.
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PMID:Identification of the cellular protein encoded by the human Wilms' tumor (WT1) gene. 133 52

Endothelial cells form a highly differentiated tissue on the inner surface of blood vessels. One of the typical characteristics is the expression of von Willebrand Factor, a protein that participates in blood coagulation. The in vitro cultivation of endothelial cells is limited by the fact that primary cells become senescent after 40 generation doublings. We have immortalized human endothelial cells by somatic cell hybridization. Primary cells were fused to different tumor cell lines of murine and human origin. The degree of differentiation of the resulting hybrids was analyzed by characterizing the expression of von Willebrand Factor. This protein was identified intracellularly and in the culture supernatant. During long-term cultivation the hybrid cells showed a tendency to lose this differentiated property even after several subcloning steps. However by fusing them with primary endothelial cells a second time, cell lines expressing von Willebrand Factor for more than 180 population doublings were generated.
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PMID:Stability of von Willebrand factor secretion in different human endothelial hybrid cell lines. 136 1

We have constructed genes expressing single-chain antigen binding proteins (scFv) which recognize the human erbB-2 receptor. These genes encode the heavy and light chain variable domains of an erbB-2 receptor specific monoclonal antibody, MAb FRP5, connected by a peptide linker. In order to express a bifunctional molecule, a bacterial alkaline phosphatase gene was fused 3' to the scFv gene. The scFv(FRP5) and scFv(FRP5)-alkaline phosphatase fusion protein (scFv(FRP5)-PhoA) expressed in E. coli specifically recognize the human erbB-2 protein and compete with MAb FRP5 for binding to the receptor. The bound scFv(FRP5)-PhoA protein can be detected directly on tumor cells using a substrate for alkaline phosphatase, showing that the chimeric protein retains both binding and enzymatic activity.
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PMID:Construction, bacterial expression and characterization of a bifunctional single-chain antibody-phosphatase fusion protein targeted to the human erbB-2 receptor. 136 87

Loss of growth regulation by transforming growth factor-beta (TGF-beta) may be an important step in carcinogenesis. We have used a cell fusion system to show that inhibition of growth by TGF-beta can be restored to carcinoma cell lines that are unresponsive to the inhibitory effects of TGF-beta. In a previous study, the EJ bladder carcinoma line was fused to the SW480 colon adenocarcinoma line and found to produce nontumorigenic hybrid cells along with one hybrid cell clone of low tumorigenicity. Here we show that the capacity of the nontumorigenic hybrid cells to respond to either TGF-beta 1 or TGF-beta 2 has been restored, while the parental or tumorigenic hybrid cells show little or no inhibition of growth following TGF-beta treatment. Cross-linking analyses with labeled TGF-beta 1 demonstrated much higher levels of the type II (85 kDa) receptor in the hybrid cells compared with the parental tumor lines. Both the parental and tumorigenic hybrid cell lines were capable of responding to TGF-beta as evidenced by increased levels of mRNA for fibronectin, type IV collagenase, and plasminogen activator inhibitor after treatment with TGF-beta 1. These results suggest that the type II receptor is necessary for mediating the effects of TGF-beta on inhibition of growth but not on gene activation of the hybrid cells.
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PMID:Inhibition of growth by transforming growth factor-beta following fusion of two nonresponsive human carcinoma cell lines. Implication of the type II receptor in growth inhibitory responses. 137 Aug 26

It has recently been shown that chimeric toxins composed of acidic fibroblast growth factor fused to mutant forms of Pseudomonas exotoxin (aFGF-PE) are cytotoxic to a variety of tumor cell lines with FGF receptors. Although aFGF-PE might be considered as a possible chemotherapeutic toxin, limited knowledge is available concerning its effect on endothelia. This study investigates whether one of the aFGF-PE fusion proteins, aFGF-PE664GluKDEL, can function as an anti-angiogenic agent. Protein synthesis studies using rat epididymal fat pad microvascular endothelial cells (RFCs) indicated that after 24 h in culture, aFGF-PE had a significant inhibitory effect on protein synthesis at concentrations greater than 100 ng/ml. In cultures incubated with 1000 ng/ml aFGF-PE, RFC protein synthesis was inhibited as much as 83%. RFCs were also cultured in a 3-dimensional type I collagen gel and incubated with either transforming growth factor beta 1, aFGF-PE, or a combination of both. Transforming growth factor beta 1 elicits in vitro angiogenesis in these 3-dimensional cultures which consist of rapid formation of complex tubular structures. Transforming growth factor beta 1-treated RFCs incubated with aFGF-PE were unable to produce this angiogenic response, nor were they able to migrate out of the 3-dimensional culture to form a monolayer as shown by controls. Cell viability analyses showed that aFGF-PE produced a dose-dependent toxic effect which ranged from 10 to 90% cell death. Competition assays in which the chimeric toxin was preincubated with antibodies to aFGF resulted in an 89% reversal of the inhibitory effects of aFGF-PE on endothelial cells. Acidic FGF-PE with a mutation in the ADP ribosylation domain of PE was inactive in both 2-dimensional and 3-dimensional cultures. These data show that aFGF-PE has specific in vitro cytotoxic, antiangiogenic, and antimigratory effects on microvascular endothelia.
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PMID:Acidic fibroblast growth factor-Pseudomonas exotoxin chimeric protein elicits antiangiogenic effects on endothelial cells. 138 Dec 75

Peritoneal mesotheliomas are uncommon among cows although there has been an increase in the frequency of diagnosis of this neoplasia in the past few years. The case of a 2 year old cow is described. On post-mortem examination, several nodules of variable size were found in the peritoneal cavity. These nodules fused together, but they did not go deep into the organs. Histologically, such nodules were formed by a population of fusiform cells of malignant morphological character and sarcomatous appearance. Immunocytochemical study, using P.A.P. techniques, showed a highly positive reaction towards vimentin and a negative reaction towards wide-spectrum cytokeratins, hence suggesting a mesenchymal origin of the neoplasia. According to the histopathological study, a multifocal peritoneal mesothelioma of sarcomatous appearance was identified.
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PMID:Immunocytochemical identification of a bovine peritoneal mesothelioma. 141 92

From June, 1989 to March, 1991, 24 cases with various spinal disorders were treated in our department using the Dick technique. The results were as follows: In the fresh fracture group (7 cases), all the spine fractures were reduced anatomically: the 2 cases without neurological defects returned to work 3 months after operation; the 3 cases with incomplete paraplegia had rapid neurological recovery; and the 2 cases with complete paraplegia showed no recovery after operation. In the late fracture group (10 cases), traumatic kyphotic curves were partially reduced and back pain was decreased markedly in all: Muscle power was increased significantly in 3 cases; spasticity was remarkably improved in 2 cases; 3 cases obtained complete cure of incontinence; and 4 cases had no significant improvement. In 3 cases with ankylosing spondylitis, the initial average kyphotic curve was 73.3 degrees, while the postoperative average curve was 28.3 degrees. The result of treatment of spinal stenosis due to degenerative spondylolisthesis (1 case) was good; slipping vertebrae were stabilized and fused with the Dick system after thorough decompression. In 1 tumor and 2 Tb-spine cases, the patients recovered and were ambulatory soon after operation.
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PMID:The application of Dick instrumentation in spine surgery. 142 57

The central region of the N-myc protein has a characteristic amino acid sequence EDTLSDSDDEDD, which is very similar to those of particular domains of adenovirus E1A, human papilloma virus E7, Simian virus 40 large T, c-myc and L-myc proteins. Domains of these three viral oncoproteins have recently been shown to be specific binding sites for the tumor-suppressor gene retinoblastoma protein. We have noted that the sequence of serine followed by a cluster of acidic amino acids is exactly the same as that of a typical substrate of casein kinase II (CKII). Therefore, we investigated whether these nuclear oncoproteins are phosphorylated by CKII. For this purpose, we fused the beta-galactosidase and N-myc genes including this domain and expressed it in Escherichia coli cells. Several mutant N-myc genes, containing single amino acid substitutions in this domain, were also used to produce fused proteins. Strong phosphorylation by CKII was detected with the fused protein of wild-type N-myc. However, no phosphorylation of beta-galactosidase itself was observed and the phosphorylations of fused mutant proteins were low. Another fused N-myc protein containing most of the C-terminal region downstream of this acidic region was not phosphorylated by CKII. Analysis of phosphorylation sites in synthetic peptides of this acidic region identified the major sites phosphorylated by CKII as Ser261 and Ser263. On two-dimensional tryptic mapping of phosphorylated N-myc proteins, major spots of in vitro-labeled and in-vivo-labeled N-myc proteins were detected in the same positions. These results suggest that two serine residues of the acidic central region of the N-myc protein are phosphorylated by CKII in vivo as well as in vitro. The functional significance of this acidic domain is discussed.
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PMID:Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II. 142 1

A rapid separation of polyamines and some related amino acids in cultured tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection is demonstrated. 60 cm x 75 microns I.D. fused-silica capillary was used for the separation and quinine sulfate was used as a background electrolyte (BGE). Several polyamines (putrescine, spermidine and spermine), amino acids (lysine, arginine, histidine) and simple cations (K+, Na+) were easily separated in less than 10 min. Using the indirect photometric detection method, femtomole amounts of polyamines extracted from the tumor cells were detected from nanoliter injection volumes, and the signal response was linear over two orders of magnitude.
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PMID:Indirect photometric detection of polyamines in biological samples separated by high-performance capillary electrophoresis. 143 36

Three cases of cementoblastoma (CB) and three cases of osteoblastoma (OB) were histologically compared. The aim of the study was to investigate whether CB and OB are different in other aspects than being connected with a tooth. CB cases were the following: maxillary lesions in a 23-year-old woman and a 22-yr-old man and a mandibular lesion in a 28-yr-old man. In one case the tumor was fused to the roots of two teeth. Of the OB cases, one occurred in the mandible of a 27-yr-old man, one in the ankle of a 19-yr-old male and one in the thoracic vertebrae of a 27-yr-old man. Histologically, CB and OB had the same appearance including peripheral spiculae rimmed by swollen blasts. This histologic similarity between OB and CB indicates that the diagnosis CB should not be made unless the lesion is connected with a tooth.
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PMID:Cementoblastoma and osteoblastoma: a comparison of histologic features. 143 31


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