Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of cancer-associated antigen 72-4 (CA72-4) (tumor-associated glycoprotein 72; TAG-72) from 106 patients with primary ovarian cancer were measured by an immunoradiometric assay employing the monoclonal antibodies (MAbs) B72.3 and CC49. Immunohistochemical localization of TAG-72 was also investigated using immunoperoxidase methodology in conjunction with both light and electron microscopy. In using a cutoff value of 4.0 U/ml for the serum assay, sensitivity of all primary ovarian carcinomas was 63.2% (67.6% of mucinous cystadenocarcinomas and 66.7% of serous cystadenocarcinomas), while specificity of benign ovarian tumors was 91.1%. Diagnostic characteristics of CA125 and CA72-4 have been demonstrated by receiver-operating-characteristics analysis. Although CA125 expressed a remarkable diagnostic efficiency with serous cystadenocarcinoma, it was less efficient with mucinous cystadenocarcinoma. CA72-4, however, was highly detectable for any histological type of ovarian cancer. Immunohistochemical staining with MAbs B72.3 and CC49 in the cytoplasm was stronger than that in the cell membrane in tissues from mucinous cystadenocarcinomas. Also, histological localization of TAG-72 in the microvilli and apical cytoplasmic membrane was demonstrated by electron microscopy using MAb B72.3 and samples of seromucinous cystadenocarcinoma (mixed type). Consequently, TAG-72 was useful for the detection of ovarian carcinoma, especially for monitoring mucinous cystadenocarcinoma, and it is localized in the microvilli and apical cytoplasmic membrane of cystadenocarcinoma cells.
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PMID:Serum and tissue measurements of CA72-4 in ovarian cancer patients. 838 75

A cancer-associated, high-molecular-weight glycoprotein antigen (6B3.Ag) recognized by monoclonal antibody 6B3 was purified from culture medium of human large cell lung carcinoma cell line (HLC-2) and characterized biochemically and immunochemically. The 6B3.Ag was purified more than 1,200-fold with a yield of 30% by salting out, precipitation by acidification at pH 4.5, and chromatographies on Sepharose 4B and concanavalin A-Sepharose. The molecular weight of 6B3.Ag is approximately 1,000,000 and the molecule is a homodecamer of 94,000 subunits. The 6B3.Ag is a glycoprotein containing 22.9% sugars, consisting of both N- and O-glycoside chains. The N-terminal 19 amino acids were determined and only 4 out of 19 amino acid residues were different from those of an antigen, L3, secreted by lung carcinoma cell line Calu-1. The serum level of 6B3.Ag was determined in normal adults as well as patients with various diseases by enzyme-linked immunosorbent assay. The mean serum level of 6B3.Ag was 3.1 micrograms/ml, ranging from 1.6 to 6.2 micrograms/ml in 131 healthy adults. When the cut-off value was set at 6.2 micrograms/ml, the incidence of positive values in the sera was elevated not only in malignant diseases such as hepatoma (73%) and leukemia (62%), but also in benign diseases such as chronic hepatitis (42%) and liver cirrhosis (63%). While the incidence of positive values was elevated in advanced liver diseases, namely, chronic hepatitis, liver cirrhosis and hepatoma, the cancer specificity of 6B3.Ag did not appear to be high.
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PMID:Detailed characterization of a high-molecular-weight glycoprotein secreted by lung cancer cells. 840 67

A single intraperitoneal dose of 300 mg/kg of p-bromophenylacetylurea (BPAU) induced progressive distal neuropathy in rats, prominently involving peripheral nerves and long central nervous system myelinated tracts such as the fasciculus gracilis and spinocerebellar pathways. Clinical signs assessed using a Functional Observational Battery (FOB) and in-cage observation included weakness and deficits in motor and sensory integration, definitively noted on post-dosing day 7. The signs were more pronounced upon repetition of the FOB on post-dosing day 12. The neuropathological substrate of these signs was a progressive axonopathy with regional swelling, leading to Wallerian-like degeneration of affected myelinated fibers. Immunocytochemical staining for synaptophysin revealed often striking increase in immunoreactivity for this synaptic vesicle glycoprotein in swollen and otherwise injured axons. Such accumulations were considered consistent with interruption of anterograde (and possibly retrograde) fast axonal transport systems secondary to toxicant-induced nerve fiber breakdown.
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PMID:Synaptophysin immunoreactive axonal swelling in p-bromophenylacetylurea-induced neuropathy. 921 98

The human tumour associated cancer antigen CA 125 is a glycoprotein with high molecular weight. The determination of this antigen has been proven to be useful in the monitoring of patients with ovarian cancer. OPUS OV, the tumour marker assay for the ovarian cancer antigen CA 125 is an ELISA that was developed for the family of fully automated random-access analyzers, OPUS, OPUS Plus and OPUS I Magnum. The assay uses a double monoclonal sandwich format (antibodies B27.1 and B43.13, Biomira/Canada). The first antibody is immobilized on the solid phase of the OPUS modules. Sample is automatically added and incubated for 5 minutes. The addition of a solution of the second antibody conjugated to the enzyme alkaline phosphatase leads to the formation of a sandwich complex within 5 minutes. The last step, the addition of the fluorogenic substrate 4-methylumbelliferyl phosphate, serves both as washing procedure and for the development of the fluorescence signal (kinetic measurement). OPUS OV has an assay range from 0-1000 kU/L with a detection limit of 5 kU/L. Within run cv's are 6-8%. A good correlation was found to commercially available kits for the determination of CA 125. We conclude that this new OPUS OV assay is a valid alternative for use in the routine determination of the cancer associated antigen CA 125 and allows more reliable determinations in terms of random access, speed, and ease of operation.
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PMID:A new tumour marker assay for ovarian cancer on the OPUS immunoassay system. 932 99

Cancer is consistently associated with anorexia. The Lobund-Wistar rat model of prostate cancer exhibits clinical manifestations (including anorexia) that resemble many aspects of the human disease. Cytokines are proposed to be involved in cancer-associated anorexia. Here we investigated mRNA profiles of feeding-modulatory cytokines and neuropeptides in specific brain regions of anorectic Lobund-Wistar rats bearing prostate adenocarcinoma tumor cells. Interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), tumor necrosis factor-alpha, transforming growth factor-beta1, glycoprotein 130 (IL-6 receptor signal transducer), proopiomelanocortin (POMC, opioid peptide precursor), and neuropeptide Y (NPY) mRNAs were analyzed with sensitive and specific RNase protection assays. The same brain region sample was assayed for all components. The data show that early anorexia in tumor-bearing rats was associated with an upregulation of IL-1beta mRNA in the brain regions examined (cerebellum, cortex, and hypothalamus). IL-1 receptor antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also significantly increased in the cortex and hypothalamus. All other cytokine components, POMC, or NPY mRNA levels were not significantly different between tumor-bearing and pair-fed (control) rats. IL-1beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rats. These data suggest that 1) IL-1beta mRNA upregulation in the brain may be relevant to the anorexia exhibited by the tumor-bearing Lobund-Wistar rat and 2) in vivo characterization of cytokine components in discrete brain regions during cancer is necessary to understand underlying molecular mechanisms responsible for cancer-associated neurological manifestations.
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PMID:Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells. 968 94

Thrombin-treated tumor cells induce a metastatic phenotype in experimental pulmonary murine metastasis. Thrombin binds to a unique protease-activated receptor (PAR-1) that requires N-terminal proteolytic cleavage for activation by its tethered end. A 14-mer thrombin receptor activation peptide (TRAP) of the tethered end induces the same cellular changes as thrombin. Four murine tumor cells (Lewis lung, CT26 colon CA, B16F10 melanoma, and CCL163 fibroblasts) contain PAR-1, as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). B16F10 cells did not contain the two other thrombin receptors, PAR-3 and glycoprotein Ib. TRAP-treated B16F10 tumor cells enhance pulmonary metastasis 41- to 48-fold (n = 17). Thrombin-treated B16F10 cells transfected with full-length murine PAR-1 sense cDNA (S6, S7, S14, and S22) enhanced their adhesion to fibronectin 1.5- to 2.4-fold (n = 5, P <.04), whereas thrombin-treated wild-type cells do not. S6 (adhesion index, 1.5-fold) and S14 (index, 2.4-fold) when examined by RT-PCR and Northern analysis showed minimal expression of PAR-1 for S6 over wild-type and considerable expression for S14. Immunohistochemistry showed greater expression of PAR-1 for S14 compared with wild-type or empty-plasmid transfected cells. In vivo experiments with the thrombin-treated S14 transfectant showed a fivefold to sixfold increase in metastases compared with empty-plasmid transfected thrombin-treated naive cells or S6 cells (n = 20, P =.0001 to .02). Antisense had no effect on thrombin-stimulated tumor mass. Thus, PAR-1 ligation and expression enhances and regulates tumor metastasis.
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PMID:Protease-activated receptor 1 (PAR-1) is required and rate-limiting for thrombin-enhanced experimental pulmonary metastasis. 980 63

Transgenic mice expressing HIV-1 coat glycoprotein gp120 in brain glial cells were previously shown to display AIDS dementia-like neuropathological changes and reduced hippocampal long-term potentiation. In this report, neuromotor and cognitive performance in 3- and 12-month-old gp120-expressing mice was compared with wildtype controls. Rotarod and cage activity measures showed no significant differences between transgenic animals and controls of either age. Open field activity was slightly altered in 12-month-old gp120 animals (reduced corner crossings and dwell in centre), but not in the 3-month-olds. Cognitive assessment using the Morris water maze showed unimpaired performance in 3-month-old mice during acquisition and (no-platform) probe trials. In 12-month-old gp120 animals, escape latency and swimming velocity during the acquisition trials were significantly reduced, but performance improved at roughly the same rate as in control animals. However, the probe trials revealed a highly significant reduction in spatial retention in transgenic mice of this age. This demonstration of age-dependent impairments in open field activity and spatial reference memory may relate to cognitive and neuromotor deficits seen in a proportion of HIV-1-infected individuals.
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PMID:Age-related behavioural deficits in transgenic mice expressing the HIV-1 coat protein gp120. 1059 67

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage.
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PMID:Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix. 1099 78

Cancer is frequently associated with anorexia, weight loss, negative nitrogen balance, and skeletal-muscle wasting. Depletion of skeletal-muscle mass is critical to overall survival of the patient, can prolong rehabilitation to normal function after recovery, and decreases quality of life in a palliative-care setting. The biochemical and physiologic bases of cancer-associated muscle wasting have been most fully investigated in animal models. These studies provide evidence for suppressed protein synthesis and activated proteolysis in cancer-associated muscle wasting and indicate a need for both anabolic and anticatabolic therapies. Several humoral factors of host or tumor origin are implicated in altered muscle-protein metabolism, including cytokines, metabolites of arachidonic acid, and a proteolysis-inducing glycoprotein; their interrelationships are less well characterized. Several catabolic mediators may share common downstream mechanisms because they ultimately activate the ATP-, ubiquitin-, and proteasome-dependent intracellular proteolytic system. Although important gaps in our current understanding remain, data available from animal studies can be used as a basis to develop relevant studies in human subjects.
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PMID:Regulation of skeletal-muscle-protein turnover in cancer-associated cachexia. 1105 10

Tn, sialosyl-Tn and T antigens are simple mucin-type carbohydrate antigens that may be expressed in human neoplasies due to alteration of the glycoprotein biosynthetic pathway. Utilising specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1), we have investigated the expression of these simple mucin-type carbohydrate antigens in large intestine of 8 human foetuses at early gestational age (9-10 weeks), obtained after therapeutic abortion. In all cases the expression of Tn antigen was mainly localised as a thin rim at the cell membrane and occasionally in the supranuclear region of epithelial cells, while sialosyl-Tn antigen was documented in some goblet cell vacuoles and occasionally in the cytoplasm of columnar cells. T antigen was not expressed in any case. These results indicate that Tn and sialosyl-Tn antigens are expressed as early as nine weeks of gestation, further supporting the notion that they may be considered as oncodevelopmental cancer-associated antigens in the large intestine.
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PMID:Expression of Tn, sialosyl-Tn and T antigens in human foetal large intestine. 1121 61


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