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

DNA content and sensitivity of DNA in situ to denaturation by acid were analyzed by flow cytometry of cell nuclei freshly isolated from the bladder tumors of 32 patients and were compared with normal urothelium of 8 subjects. DNA sensitivity to denaturation was assessed in RNase treated cells by acridine orange metachromasia following partial denaturation with hydrochloric acid; the extent of denatured DNA is given as an index (alpha t), representing the ratio of single stranded to total DNA per nucleus. Of the low stage tumors (papillomas, Ta, Tis, T1) 11 of 18 (61%) were aneuploid. Of the high stage tumors (T2 and T3a) 11 of 14 (79%) were aneuploid. DNA in nuclei of normal transitional epithelium was very sensitive to denaturation, as was papilloma, characterized by nuclear alpha t indices of 0.73 +/- 0.01 (SD) and 0.73 +/- 0.04, respectively. Nuclear DNA of noninvasive carcinomas (Ta, Tis) was significantly more resistant to denaturation (alpha t = 0.69), and DNA of invasive carcinomas was most resistant, ranging from alpha t = 0.61 (T1 tumors) to alpha t = 0.59 (T2 tumors) to alpha t = 0.57 (T3 tumors). High stage tumors as a group (T2, T3) had significantly different (lower) alpha t values than low stage tumors (Ta, Tis, T1). In model cell culture systems it is known that a decrease in alpha t index, i.e., greater resistance to denaturability, occurs as cells transit from resting phase into the cell cycle. Whether the alpha t index can be used to estimate resting vesus cycling cells of human tumors is still speculative; changes in DNA denaturability also are known to occur with changes in chromatin structure during cell differentiation and in transformation. However, the empirical relationship between alpha t index and tumor stage, of itself, may prove clinically useful in identifying more advanced and perhaps more aggressive tumors.
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PMID:DNA in situ sensitivity to denaturation in bladder cancer and its correlation with tumor stage. 225 31

This paper addresses the expression of the epidermal growth factor (EGF) gene by human breast tumor biopsy samples. Northern analysis was used to demonstrate the presence of an approximately 5-kilobase mRNA which specifically hybridized with radiolabeled human EGF complementary DNA in some human breast tumor biopsy samples. Quantitation of EGF mRNA in 60 human breast tumor biopsies using the RNase protection assay revealed that 83% of tumors contained detectable EGF mRNA. Estrogen receptor (ER) and progesterone receptor (PgR) mRNAs were similarly quantitated in the same samples. It was found that 89.4% of the ER mRNA-positive breast tumor biopsies had detectable EGF mRNA, whereas only 58.3% of the ER mRNA-negative tumors had detectable EGF mRNA. Furthermore, whereas 90.5% of the PgR mRNA-positive tumors contained EGF mRNA, only 60% of the PgR mRNA-negative tumors contained EGF mRNA. chi 2 analysis indicated that the increased percentage of tumors expressing EGF in the receptor-positive groups was statistically significant (P less than 0.01). It was also found that the mean relative level of EGF mRNA in those tumors which were ER and PgR negative [9.8 +/- 5.6 (SEM) relative units] was significantly lower than those tumors which were ER and PgR positive (40.5 +/- 6.4 relative units, P less than 0.05) or ER positive and PgR negative (68.4 +/- 19.9 relative units, P less than 0.005). These observations suggest that the EGF-expressing tumors probably arose originally from hormonally responsive cell types and that EGF expression in a large proportion of human breast tumors in vivo may also be hormonally responsive.
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PMID:Epidermal growth factor gene expression in human breast cancer biopsy samples: relationship to estrogen and progesterone receptor gene expression. 236 77

This investigation sought to characterize biochemically the tumor-specific transplantation antigens (TSTA) expressed on the cell surface of a panel of chemically induced fibrosarcomas of C3H/HeJ mice. Results suggest a uniform antigenic framework upon which individual specificities are superimposed. The antigens expressed by the 3-methylcholanthrene-induced fibrosarcomas MCA-D, MCA-F, and MCA-2A fulfill the requirements of a TSTA; namely, immunization of syngeneic hosts with irradiated cells or soluble extracts engenders a tumor-specific immune response such that animals resist challenge with the same, but not another, tumor. Brief incubation of intact tumor cells in single-phase aqueous solutions of 2.5% (v/v) 1-butanol extracts an immunoprotective TSTA, but not alloantigenic activity, from MCA-F cells. This extraction protocol was extended to the two other MCA-induced neoplasms. The butanol-extracted TSTA from the three tumors displayed isoelectric pHs of 6.4 to 6.6 following preparative isoelectric focusing. The tumor-specific immunoprotective activity from all three tumors displayed an apparent molecular weight of 150,000 (150 kDa) during high-performance gel permeation chromatography. The chromatographic properties of the 150 kDa antigens were unaffected by reduction using dithiothreitol, but incubation in acetate buffer, pH 3.0, dissociated the 150 kDa complex into at least two components with molecular weights of 70 to 100 kDa and 20 to 40 kDa. Only the smaller component displayed TSTA activity. The presence of two major components in the 150-kDa antigen was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TSTA activity was sensitive to digestion with pronase, papain, chymotrypsin, and alpha-mannosidase, but resistant to DNase, RNase, neuraminidase, trypsin, endoglycosidase H, and a mixed-function glycosidase. In addition, the TSTA activity was unaffected by heating. These data demonstrate that MCA carcinogenesis results in the expression of immunologically unique epitopes on biochemically related glycoproteins and suggest a unified mechanism for the generation of TSTA polymorphism.
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PMID:Biochemical characterization of 1-butanol-extracted murine tumor-specific transplantation antigens. 240 45

Pyronin Y (PY) is an intercalating cationic dye that shows specificity towards RNA. In viable cells this dye also accumulates in mitochondria. The cytostatic and cytotoxic effects of PY on L1210 and Chinese hamster ovary cells were studied in relation to its intracellular localization and compared with the affinity of PY to bind to double-stranded DNA and RNA and its propensity to condense single-stranded DNA and RNA. Antitumor properties of PY were tested on L1210 leukemia and Sarcoma 180 ascites in mice. At a concentration of 1.7 to 3.3 microM, PY was localized almost exclusively in mitochondria of cultured cells, similar to another mitochondrial probe, rhodamine 123. At that concentration PY was not toxic but suppressed cell growth, arresting cells in G1. At a concentration of 6.7 to 33.0 microM, PY was also localized in nucleoli and uniformly in cytoplasm, bound to the RNase-sensitive material therein. At that high concentration PY induced cell arrest in G2 and S and was cytotoxic. The dye exhibited a propensity to bind and condense (precipitate) single-stranded nucleic acids, and condensation could be measured by the appearance of light-scattering products. Among a variety of natural and synthetic nucleic acids the most sensitive were the RNA polymer, polyriboadenylate, and the copolymer, polyriboadenylate and polyriboguanylate, which underwent condensation at a PY concentration of 6.6 to 10.0 microM. Natural and synthetic DNA polymers were resistant to condensation. The data suggest that the cytostatic (G2 and S arrest) and cytotoxic (inability to exclude trypan blue, loss of clonogenicity) effects of PY seen at 6.7 to 33.0 microM concentration may be a consequence of the dye binding to RNA. PY may intercalate to double-stranded RNA and/or cause the specific condensation of single-stranded RNA; the polyadenylated sections of mRNA appear to be the most sensitive cellular targets to undergo condensation. PY showed antitumor properties extending survival of L1210 leukemic mice by 50% and slowing growth of Sarcoma 180 ascites tumor. The possibility that certain antitumor drugs, generally believed to act via intercalation to DNA, may exert chemotherapeutic effects via their interactions with RNA is discussed.
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PMID:Cytostatic and cytotoxic properties of pyronin Y: relation to mitochondrial localization of the dye and its interaction with RNA. 242 84

The chicken c-myc gene is the target for proviral insertion mutations in bursal lymphomas and has been transduced to generate several viral oncogenes, but the boundaries of its exons have not been securely established. To define the landmarks of the chicken c-myc gene necessary to produce its mRNA, we used an RNase protection assay and a cDNA clone to analyze the c-myc mRNAs from normal chicken embryos and from two bursal lymphomas: LL6, which contains an avian leukosis virus provirus downstream of the c-myc coding region, and LL7, which contains an avian leukosis virus provirus upstream of the c-myc coding region. Two initiation sites for normal c-myc mRNA are less than 7 bases apart, downstream of a GC-rich region lacking canonical TATA and CAAT sequences. The first exon has two open reading frames for the entire length but no initiator methionine codons. The splice donor and acceptor sites at the boundary of the first intron were assigned by comparing a sequence of an LL6 c-myc cDNA clone with a genomic DNA sequence and confirmed by RNase protection of labeled RNA probes by normal and LL6-derived mRNAs. Two potential polyadenylation signals are located approximately 250 and 400 bases downstream of the c-myc coding region in the third exon, but only the more distal signal is utilized in both normal cells and the LL7 tumor. The proviral integration in the LL6 tumor occurred upstream of the authentic c-myc polyadenylation signal accounting for polyadenylation of this transcript in the proviral long terminal repeat.
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PMID:Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas. 243 Dec 93

We have investigated the requirements for the induction of the acute phase response to inflammation using the FAZA rat hepatocyte cell line which can be induced to activate the acute phase response genes with supernatants from human or rat monocytes. Using ribonuclease mapping of fibrinogen transcripts, we find that the tumor promoter 12-O-tetradecanoylphorbol-13-acetate can induce a 10-20-fold increase in properly initiated and spliced fibrinogen mRNA. This response is likely to be mediated by protein kinase C (Ca2+/phospholipid-dependent enzyme) since the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol, can also induce fibrinogen mRNA. In addition to the alpha, beta, and gamma chains of fibrinogen, other acute phase response mRNAs are induced by 12-O-tetradecanoylphorbol-13-acetate including alpha 2-macroglobulin. The active agent capable of inducing the fibrinogen mRNAs in the monocyte supernatants is clearly not interleukin 1 (IL-1) or tumor necrosis factor. The FAZA cell line does not have detectable IL-1 receptors and does not respond to either murine or human IL-1 or the 30-kDa precursor for IL-1. In addition, fibrinogen cannot be induced by tumor necrosis factor alpha in this cell line, and the active agent in monocytes supernatants cannot be neutralized with polyclonal or monoclonal antibodies to tumor necrosis factor alpha. We conclude that a third as yet uncharacterized agent is responsible for the induction of fibrinogen during the acute phase response and that this agent transduces its signal to the fibrinogen genes by a mechanism involving protein kinase C.
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PMID:Induction of fibrinogen and a subset of acute phase response genes involves a novel monokine which is mimicked by phorbol esters. 244 Aug 78

A nucleic acid-rich fraction extracted and purified from BCG (MY-1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti-viral activity and rendered normal macrophages cytotoxic towards tumor cells. These cellular responses were induced by the MY-1 digested preliminarily with RNase, but not by the MY-1 digested with DNase, indicating that DNA contained in MY-1 was essential for the responses. The function of the factor to activate macrophages was destroyed by treatment with a small amount of anti-interferon (IFN)-gamma antiserum or under acidic conditions (pH 2), but not by treatment with anti-IFN-alpha/beta antiserum, while the anti-viral activity was destroyed almost completely by treatment with anti-IFN-alpha/beta antiserum. It appears that DNA from BCG stimulated mouse spleen cells in vitro, resulting in augmentation of NK activity and production of IFN-alpha/beta and -gamma.
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PMID:In vitro augmentation of natural killer cell activity and production of interferon-alpha/beta and -gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG. 245 94

An analysis of the human estrogen receptor (ER) mRNA was performed on 71 human breast tumors using an RNase protection assay. Complementary DNA clones to the human estrogen receptor (lambda R8 and lambda R3) were used to generate small antisense 32P-labeled RNA molecules that were hybridized to the tumor RNA. We determined the relative amounts of ER mRNA in each tumor by measuring the amount of RNases A and T1 resistant hybrids. Moreover, because RNase A has the ability to cleave single-base mismatches within RNA/RNA duplexes, we were able to use the assay to screen for possible mutations or deletions in the ER mRNA. A significant correlation was found between the ER mRNA levels and the estrogen binding concentrations determined by a dextran-coated charcoal assay (r = 0.68; P less than 0.0001; n = 58). We also identified a subpopulation of tumors in which a mismatch in the ER mRNA was detected. This message modification, in the B region of the message, significantly correlated with low levels of estrogen binding. This result suggests that the observed B variant might lead to the production of receptors with altered properties.
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PMID:A variant estrogen receptor messenger ribonucleic acid is associated with reduced levels of estrogen binding in human mammary tumors. 245 5

Studies on the time-course utilization of radiolabeled pyridoxine in rats with hepatomas led to the discovery of a novel vitamin B6 product. It is found in a spectrum of tumor lines but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20-30% of labeled pyridoxine into the novel product. Its structure was tentatively identified as adenosine-N6-methyl, propylthioether-N-pyridoximine-5'-PO4. However, results of tests on the incorporation of labeled precursors into the novel product by 3B3 hybridoma or HL-60 cells support an N6-diethylthioether bridge linking the adenosyl and pyridoxyl moieties. The synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine is reported in this paper. The mass spectrum of this analog is similar to that of the tumor product as seen by its fragmentation in further support of the structure of the tumor product. Whether the latter may be part of tumor RNA is questionable. RNA was isolated for 3B3 or HL-60 cells after incubation with tritiated or 14C-pyridoxine using SDS-phenol repeated extractions in the presence of RNase inhibitors. Centrifugation of cRNA on 5-20% linear sucrose density gradients showed practically all the label at the top of the gradient. RNase treatment resulted in a labeled product which coeluted with the tumor product on reverse phase paired-ion HPLC and chromatographed as dinucleotide on paper. These results suggest that the novel tumor product may occur as a short oligonucleotide.
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PMID:Synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine: an analog of a novel vitamin B6 tumor product. 251 52

To determine the pattern of alternative splicing at the 5' end of class I genes, the 3' splice sites bordering exon 2 of the H-2Dd and H-2Kd genes were mutated from AG to GG (H-2Dd) or CG (H-2Kd). The mutant genes were transfected into L cells, and RNA from clones expressing these Ag was used for analysis by RNase and S1 nuclease mapping techniques. The first intervening sequence of both class I genes contains several potential 3' splice acceptor sites. However, a clear preference for only one site was detected in each of the H-2Dd and H-2Kd mRNA. Examination of the endogenous H-Dd and H-2Kd class I transcripts in normal murine tissues and in tumors demonstrated that the alternatively spliced mRNAs were produced, but at a low frequency. Infection of transfected L cells or tumor lines with vesicular stomatitis virus altered the level of differentially spliced message in these cells.
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PMID:Mutation of 3' splice sites in two different class I genes results in different usage of cryptic splice sites. 254 75


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