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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the isolation and identification of the RNA specifically immunoprecipitated and covalently linked to the tumor suppressor gene product p53. After treatment with proteinase K, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) band of p53 yields a single, discrete 157-nucleotide RNA, which was cloned, sequenced, and identified as 5.8S rRNA. 5.8S rRNA was obtained only after proteolysis of the p53 SDS-PAGE band. Free 5.8S rRNA did not comigrate with p53 in SDS-PAGE. This RNA was only immunoprecipitated from cells containing p53. Protein-free RNA obtained by proteolysis of the p53 band hybridized to the single-stranded DNA vector containing the antisense sequence of 5.8S rRNA. The covalence of the p53-5.8S rRNA linkage was demonstrated by the following findings: (i) p53 and the linked 5.8S rRNA comigrated in SDS-PAGE; (ii) only after treatment of the p53-RNA complex with proteinase K did the 5.8S rRNA migrate differently from p53-linked 5.8S rRNA; and (iii) this isolated RNA was found linked to phosphoserine, presumably at the 5' end. Covalent linkage to the single, specific RNA suggests that p53 may be involved in regulating the expression or function of 5.8S rRNA.
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PMID:p53 is covalently linked to 5.8S rRNA. 140 86

NADPH cytochrome c (P-450) reductase was purified from human placental microsomes using a combination of affinity and gel filtration chromatography. Affinity chromatography using agarose-hexane-adenosine 2'5 diphosphate resulted in two protein bands being detected by SDS-PAGE of approximate MwS 68 and 75 kDa. Fractions containing the two proteins were pooled, and then resolved using Sephacryl S-200. Both of the purified proteins displayed enzyme activity, measured by their ability to reduce cytochrome c. The 75 kDa protein obtained was used to immunize three female New Zealand white rabbits. The IgG fraction was partly purified from rabbit sera which suppressed placental microsomal NADPH cytochrome c reductase activity by > 80% using 33% ammonium sulphate. The procured antibody suppressed androstenedione aromatase activity in microsomal preparations of human placental and breast adipose tissue, and NADPH cytochrome c reductase activity in prostate (benign and malignant), MDA-MB-231 breast cancer cells, breast adipose, Hep G2 hepatoma cells and placental microsomal preparations. The extent of NADPH cytochrome c reductase inhibition varied in the order of malignant prostate < benign prostate < MDA < breast adipose < Hep G2 < placenta. The results suggest that human placental NADPH cytochrome c (P-450) reductase shares common antigenic epitopes pertinent to its capability of reducing cytochrome c in all of the above-mentioned tissues. In attempting to associate possible changes in NADPH cytochrome c reductase activity imposed by neoplasia to the obtained immunochemical cross reactivity and enzyme activity results, it was noted that microsomes obtained from MDA cells exhibited enzyme activity significantly less than that of breast adipose microsomes (1.6 and 8.1 nmol/min/mg protein, respectively) and by comparison showed 6% less homology towards the placental antibody. The results obtained for benign and malignant prostate showed no significant difference between the neoplastic states as adjudged by enzyme activity and immunochemical assays.
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PMID:Immunochemical specificity of placental NADPH cytochrome c (P-450) reductase in neoplastic and non-neoplastic human tissue. 141 86

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.
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PMID:Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines. 142 26

A monoclonal antibody, designated MAb-5A IIgG1), was generated against a tumorigenic rat esophageal epithelial cell line, B-2T. MAb-5A reacted with a series of non-tumorigenic and tumorigenic epithelial cell lines derived from F-344 rat esophagi or tracheas. However, the highest level of antigen expression was detected on tumorigenic rat epithelial cell lines. A trace amount of antigen was detected in primary cultures of normal rat epithelial cells derived from either esophagi or tracheas. MAb-5A did not react with rat fibroblasts. MAb-5A reacted with B-2T derived tumor tissues propagated in vivo but showed only slight reactivity with normal rat esophageal epithelial tissues. Cell surface radioiodination, extraction and immunoprecipitation experiments were conducted to characterize the antigen molecule. Analysis of the immunoprecipitates by SDS-PAGE and autoradiography revealed two protein bands with mobilities corresponding to approximately 140 and 120 kDa, respectively. Under reducing conditions the 140 kDa band shifted to approximately 120 kDa whereas the 120 kDa band shifted upward to approximately 130 kDa. The non-reduced/reduced mobilities of these bands suggest that they may be members of the integrin family of matrix receptors. A polyclonal antibody to the beta 1 subunit immunoprecipitated two similar bands detected by MAb-5A, further suggesting that the antigen complex may be related to members of the integrin superfamily.
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PMID:A monoclonal antibody produced against a rat esophageal carcinoma cell line reacts with an integrin-like molecule expressed by rat epithelial cells. 145 82

Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.
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PMID:Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells. 147 74

The peanut agglutinin (PNA)-binding site is protein-bound Gal beta 1-->3GalNAc, and is a tumor-associated carbohydrate marker expressed in many human carcinomas. PNA-binding glycoproteins isolated from KATO-III human gastric carcinoma cells were deglycosylated by trifluoromethanesulfonic acid, and rabbit antibodies against the core proteins were used to screen a lambda gt11 expression library constructed from these cells. Two different core proteins were identified by this approach. One was polymorphic epithelial mucin (PEM), initially found in breast carcinomas. PEM mRNA was expressed in normal tissues of the stomach, colon, and lung, but not in the small intestine, thyroid, and spleen. High levels of PEM mRNA were detected in some nude mouse-transplanted carcinomas, i.e. colorectal, pancreatic, stomach, and lung carcinomas. The other core protein was a novel one called MGC-24, which has a molecular mass of 24 kDa, is rich in hydroxyl amino acids and cysteine, and lacks repeating motifs. The mature MGC-24 glycoprotein behaved as a high-molecular-mass one upon SDS-polyacrylamide gel electrophoresis even after neuraminidase treatment. Treatment with endo-alpha-N-acetylgalactosaminidase in the absence of neuraminidase significantly changed the staining pattern by anti-MGC-24, confirming that MGC-24 carried PNA-binding sites. MGC-24 mRNA was intensely expressed in normal tissues of the colon, small intestine and thyroid, and in some nude mouse-transplanted colorectal and pancreatic adenocarcinomas.
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PMID:A novel core protein as well as polymorphic epithelial mucin carry peanut agglutinin binding sites in human gastric carcinoma cells: sequence analysis and examination of gene expression. 147 19

Hexokinase II prepared from Ehrlich-Lettre hyperdiploid tumor cells (ELD cells) was subjected to a limited digestion by trypsin. After 60 min digestion, hexokinase II (100 kDa) was completely cleaved to two fragments with the molecular weight of about 60 kDa and 40 kDa as manifested in SDS-PAGE. It was noteworthy that the enzyme activity was observed even at the time when the native enzyme molecule was no more detectable. These fragments were separated by SDS-PAGE irrespective of the presence of a reducing agent, but neither by native PAGE nor by cellulose acetate membrane electrophoresis under the nondenaturing conditions. Neither kinetic parameters such as Km values for ATP and glucose nor an ability of binding to mitochondria were changed significantly by the tryptic digestion. These results indicate that an essential conformation of hexokinase II can be restored by the self-association of two fragments produced as a result of the cleavage by trypsin at the middle of the molecule. Affinity labeling with 2',3'-dialdehyde ATP followed by the trypsin digestion showed that ATP binding site resided in the 40 kDa fragment. Furthermore, the mode of the response in the incorporation of this ATP analog to hexose phosphate, moreover, was similar to that in the catalytic activity.
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PMID:Cleavage of hexokinase II to two domains by trypsin without significant change in catalytic activity. 148 Jan 68

B700 is a murine melanoma antigen that is closely related to, but distinct from, serum albumin. The present study examined the metabolic fate and anatomic distribution of radioiodinated B700 and mouse serum albumin (MSA) administered s.c. to mice. In blood, both proteins were associated with the plasma fraction where the halflife of B700, a glycoprotein, was 0.5 days, compared to 2.7 days for MSA. Of particular interest was the observation that B700, a 67 kD anionic protein, was excreted primarily in urine. The selective B700-proteinuria did not alter urinary volumes or produce hematuria or edema. SDS-polyacrylamide gel electrophoresis and western blot analysis using the H-2-3-3 B700-specific monoclonal antibody revealed that B700 proteinuria occurred in B-16 murine melanoma bearing animals but not in control mice. These studies demonstrate that the tumor-bearing host readily distinguishes between very similar normal protein (MSA) and tumor-associated antigen (B700) molecules and processes them differently.
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PMID:Proteinuria of B700, a 67 kD albumin-like melanoma-specific antigen. 149 72

1. Serum proteins showed quantitative and qualitative differences between sarcomatous and healthy soft shell clams, Mya arenaria L. 2. Total protein concentration was significantly higher in the serum of sarcomatous clams than of healthy clams. 3. According to SDS-PAGE, more serum proteins with more variability distinguished sarcomatous clams from healthy ones. 4. Sarcomatous clams had unique serum proteins of M(r)23,000, 45,000 and 54,000. Healthy clams had unique serum proteins of M(r) 24,000, 103,000 and 105,000. 5. During disease progression, sarcoma-specific proteins appeared while normal proteins disappeared. 6. We propose that some sarcoma-associated proteins may have tumor promoting and/or cytotoxic functions and that some normal proteins which disappear during disease progression may be involved in the humoral defense system.
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PMID:Different proteins in the hemolymph sera from sarcomatous and healthy soft shell clams, Mya arenaria L. 149 99

The highly (ASML) and non metastatic (AS) variants of the rat tumor BSp73 were compared with respect to cell surface carbohydrate proteins. Fluorescence labelling with lectins (ConA, MPA, PNA, SBA, UEA-I, WGA) revealed a differentiated carbohydrate pattern at the cell surface of these cell lines. The highly metastatic variant was significantly more glycosylated with respect to galactosyl, mannosyl and N-acetylgalactosylamine residues; fucosyl residues were exclusively expressed in the metastatic variant. Examination of isolated plasma membrane fractions showed quantitative differences with respect to glycosylated proteins separated on polyacrylamide gels. A 30 kDa glycoprotein (GP30-ASML) dominant in the metastatic variant was further characterized. Various detergents (CHAPS, Nonidet, SDS, Triton X-100) and urea extracted it exclusively from the highly metastatic variant. GP30-ASML is a predominantly O-glycosylated single polypeptide chain with terminal N-acetylgalactosamine and galactosyl residues; its molecular weight determined by SDS-PAGE is 30 kDa and its isoelectric point is 7.8. Immunofluorescence localization experiments with monoclonal antibodies specific for GP30-ASML and polyclonal antibodies raised against GP30-ASML showed this protein at the cell surface and in the lysosomal compartment of both cell lines; exclusively in the non metastatic variant it was also found in the nuclear membrane. The function of this protein is still unknown.
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PMID:Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor. 150 18


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