Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a large noncollagenous glycoprotein, laminin, from a mouse tumor that produces basement membrane. The protein consists of at least two polypeptide chains (Mr = 220,000 and Mr = 440,000) joined to each other by disulfide bonds. Laminin and type IV collagen are major constituents of the tumor. Laminin is distinctly different from fibronectin, another component of basement membranes, in amino acid composition and immunological reactivity. Pepsin digestion of laminin releases a large, cystine-rich fragment which retains most of the antigenicity of the original protein. Immunological studies using purified antibody against laminin show that it is produced by a variety of cultured cells. In addition, these antibodies react with the basement membranes of normal tissues, suggesting that this protein or an immunologically related protein is a constituent of the basement membranes of these tissues.
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PMID:Laminin--a glycoprotein from basement membranes. 11 18

Cells present in the polyoma virus-induced murine ascites tumor SEYF-a showed the capacity to fix soluble immune complexes of ovalbumin anti-ovalbumin. The fixation could be inhibited by preincubating the cells with antisera directed against H-2 antigens and with syngeneic anti-tumor antibodies. The latter did not react with normal cells. Depletion of phagocytes from the ascites cell population, thus enriching for tumor cells, increased the inhibition of complex fixation by the syngeneic anti-tumor antiserum. The inhibition of complex fixation by the anti-tumor antibodies was not mediated by "third-party" complexes. Pepsin-treated globulin derived from the syngeneic anti-tumor antiserum could still inhibit complex fixation by SEYF-a cells. These results raise the possibility that tumor cells, per se, expressed receptors for immune complexes. Macrophages, apparently of host origin, residing in the SEYF-a tumor, also expressed such receptors.
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PMID:Receptors for immune complexes on cells within a polyoma virus-induced murine sarcoma. 18 60

The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.
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PMID:Renal prostaglandins. 110 Oct 92

Parathyroid tumors may occur in a sporadic fashion or, more rarely, as part of a familial syndrome (such as familial multiple endocrine neoplasia type I). The MENI gene has been mapped by linkage analysis to chromosome 11 at band q11-q13, and presumably acts as a tumor suppressor gene. In the present study, which is an extension of our previous studies, we examined 41 parathyroid tumors from patients with familial multiple endocrine neoplasia type I and 61 sporadic parathyroid tumors with markers on chromosome 11, to assess the extent of allelic loss in those tumors. Twenty-four of the MENI-associated tumors (58%) and 16 of the sporadic parathyroid tumors (26%) displayed allelic loss from chromosome 11. The region of overlap of the allelic losses in the MENI-associated tumors enables us to place the MENI gene between PGA centromerically and INT2 telomerically, a region spanning about 7.5 cM. Taken together with locus ordering by linkage analysis, this clearly localizes the MENI gene telomeric to the PGA locus. Our inability to detect allelic loss on chromosome 11 in some parathyroid tumors suggests the existence of other genes involved in the development and/or progression of this subgroup of presumably monoclonal tumors; or that localized events involving the 11q tumor suppressor gene have occurred in some parathyroid tumors whose detection is beyond the sensitivity of our analysis; or that at least some of the specimens analyzed were in fact primarily hyperplastic parathyroid tissue.
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PMID:Allelic loss from chromosome 11 in parathyroid tumors. 136 Aug 70

Expression of the cysteine proteinase cathepsin B and its physiological inhibitor cystatin C was analyzed in vitro in 1 human fibrosarcoma and 4 human colon carcinoma cell lines. Cystatin C antigen as well as cathepsin B activity were detected in the conditioned media of the 5 cell lines. The corresponding cell extracts expressed high levels of cathepsin B activity, whereas only trace amounts of cystatin C antigen could be found. Northern-blot analysis revealed the presence in the 5 cell lines of a 0.8-kb cystatin C mRNA transcript and 2 cathepsin B transcripts of 2.3 and 4.3 kb. Pepsin treatment of tumor-cell-released cathepsin B induced an average 7.3-fold increase in activity, indicating that the enzyme was mainly present as a latent form in conditioned medium. The pepsin-activated cathepsin B from one colon carcinoma cell line was further characterized using the cysteine proteinase inhibitors E-64, recombinant cystatin C, a cystatin-C-derived peptidyl inhibitor (Z-LVG-CHN2), and cathepsin-B-specific diazomethyl ketone inhibitors (Z-FT(OBzl)-CHN2, Z-FS(OBzl)-CHN2). This activity was totally neutralized by recombinant cystatin C, suggesting a potential for interaction between released extracellular cathepsin B and cystatin C. In vitro assays of degradation of extracellular matrix showed that cysteine proteinase inhibitors could decrease matrix degradation induced by pepsin-activated conditioned media. With colon cells, this inhibition was not observed, indicating a requirement for an extracellular activation of latent cathepsin B. Our data provide evidence that cystatin C and latent cathepsin B are both released extracellularly by colon carcinoma cells in vitro. They suggest that cystatin C and cathepsin B interactions may participate, in an as yet unelucidated way, in the modulation of the invasive phenotype of human colonic tumors.
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PMID:Cystatin C and cathepsin B in human colon carcinoma: expression by cell lines and matrix degradation. 139 47

Flow cytometric DNA analysis of nuclear suspensions from formalin-fixed, paraffin-embedded tissue often fails to detect aneuploid cell populations present in corresponding fresh tissue. Nuclear suspensions were prepared by 8 different modifications and standard Hedley's method using 50-microns sections of tissue blocks from 8 breast and 8 colonic carcinomas, all previously known to be DNA aneuploid by analysis of fresh tumor. Pepsin solutions of three different enzymatic activities were used to release nuclei using three different tissue digest formats. DNA aneuploidy was demonstrated overall in 7 of 72 different colon tumor experiments and 25 of 72 breast cancer experiments. Modifications yielded aneuploid populations not detected by the standard Hedley method; DNA aneuploidy of 4 breast and 2 colon cancers was detected by modifications compared to 2 breast and 1 colon cancer demonstrated by the standard. No single method consistently demonstrated DNA aneuploidy. High histogram baselines, presumably from debris, contributed to the marked loss of sensitivity in detecting most DNA aneuploid populations. Detection of DNA aneuploidy was most closely associated with specific cases, regardless of the method of nuclear suspension preparation. Recovery of DNA aneuploid nuclei seems to depend primarily on tissue processing or innate characteristics of the tumor cells, not on the method used to prepare the nuclear suspension.
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PMID:Comparison of eight modifications of Hedley's method for flow cytometric DNA ploidy analysis of paraffin-embedded tissue. 152 60

The effects of prostaglandins (PGs) A and J, which are anti-tumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA1, PGA2, PGJ2, and delta 12-PGJ2 in similar dose-dependent fashions. The effects of PGA1 and PGA2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ2 and delta 12-PGJ2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G1/S border, was added after the removal of PGA2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c-myc mRNA formed two peaks during the G1 phase, at 1-2 h and at 8-12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18-24 h, whereas in controls, c-myc mRNA decreased quickly after entry into S phase. The rate of degradation of c-myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G1/S border, but that this inhibition is not accompanied by the reduction in c-myc gene expression in contrast with some types of tumor cells treated with PGs.
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PMID:Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression. 157 2

Earlier studies from this laboratory revealed that killer lymphocyte lineages are inactivated in the tumor-bearing host by macrophage-derived PGE2. In this study, we examined whether tumor bearing causes a change in the density or affinity of PGE2 receptors on lymphocytes, making them more vulnerable to PGE2 action, and whether it enhances PGE2 production by host macrophages. PGE2 receptors were examined on both unfractionated and monocyte-macrophage-depleted splenocytes of normal or tumor-bearing C3H/HeJ mice (at 25 days following s.c. transplantation of 10(6) C3 mammary adenocarcinoma cells) using a [3H]PGE2 binding assay in the presence of increasing (up to 10(4)-fold) concentrations of unlabeled PGE2 (or PGA or PGF2 alpha as specificity controls) followed by a Scatchard analysis. PGE2 production by splenic macrophages was measured with a radio-immunoassay. Results revealed that splenocytes in normal and tumor-bearing mice bear specific receptors for PGE2, since splenocyte binding of [3H]PGE2 (10(-9) M) was inhibited in the presence of excess unlabeled PGE2, but not 10(-4)-fold excess PGA or PGF2 alpha. Tumor-bearing did not appear to cause an appreciable change in the affinity or density of these receptors, since Kd and Bmax values for PGE2 binding were similar for normal and tumor-bearing mice. However, specific PGE2-binding by splenocytes in vitro was reduced in tumor-bearing mice. Three types of evidence indicate that this resulted from a partial occupation of PGE2 receptors on lymphocytes with PGE2 produced by splenic macrophages of tumor-bearing hosts. First, depletion of monocyte-macrophages from the splenocyte population improved this binding in tumor-bearing but not normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PGE2 receptors on murine splenic lymphocytes: effects of tumor bearing. 166 31

In a series of bronchial and bladder carcinomas, p53 protein expression was examined. Samples from formalin-fixed, paraffin-embedded tissue (routine-treated) were compared with parallel samples of fresh tissue and tissue fixed in paraformaldehyde and ethanol. The expression of p53 was measured by immunofluorescence staining and dual parameter flow cytometry, with simultaneous monitoring of DNA content. For each tumor, p53 fluorescence with different fixatives was expressed relative to fresh tissue. The p53 fluorescence signals were on average brighter from routine-treated tissue than from fresh tissue. The tissue fixed in paraformaldehyde showed no difference from fresh tissue. In the ethanol-fixed tissue, however, fluorescence signals were reduced by nearly 70%, and the fraction of detectable p53 positive cells in tumor tissue was reduced by more than 50%. This loss of fluorescence was probably due to a leakage of the antigen from nucleus to cytoplasm. Pepsin treatment did not influence p53 fluorescence. Within the same tumor, the S-phase fraction in p53 positive cells was significantly higher than in p53 negative cells (13.1 +/- 2.0% vs. 6.5 +/- 0.8%). This pattern was not influenced by formalin fixation or pepsin treatment. Our study demonstrates that in measuring a nuclear antigen, tissue handling may influence the results, and care should be taken to optimize the preparation procedure. Using the antibody PAb 1801, p53 expression measured in archival material is not reduced as compared to fresh tissue.
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PMID:Influence of tissue preparation techniques on p53 expression in bronchial and bladder carcinomas, assessed by immunofluorescence staining and flow cytometry. 178 31

Multiple endocrine neoplasia type 1 is an autosomal dominant condition characterized by the development of parathyroid hyperplasia, pituitary adenomas, and pancreatic islet cell tumors. Recently the gene for multiple endocrine neoplasia type 1 was mapped to the long arm of chromosome 11 between the loci PGA and INT2. We tested the hypothesis that tumor development is the result of a somatic deletion that unmasks a constitutional mutation. By investigating DNA isolated from tumors and somatic tissues in 12 patients from 4 different families with multiple endocrine neoplasia type 1, we found loss of heterozygous markers mapped to 11q13 in 9 (82%) of 11 informative tumors. In contrast, we were unable to identify allelic loss from other chromosomes using a variety of informative probes. This high incidence of chromosomal deletion of 11q13 suggests that this region is important in the oncogenesis of this disorder.
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PMID:Loss of heterozygosity of markers on chromosome 11 in tumors from patients with multiple endocrine neoplasia syndrome type 1. 197 36


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