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

It was shown that normal nonimmune C3H mouse spleen cells became specifically cytotoxic to chemically-induced syngeneic C3H tumor cells by incubation with xenogeneic I-RNA extracted from the lymphoid organs of specifically immunized guinea pigs. This response was specific for the tumor used to immunize the I-RNA donor. In a totally syngeneic system, we showed that syngeneic I-RNA extracted from the spleens of tumor-bearing rats mediated cytotoxic immune reactions which were directed specifically against the tumor-associated antigens of syngeneic rat tumor target cells. Active antitumor I-RNA synthesis in the lymphoid organs of I-RNA donor animals reached a maximum between days 14 and 21, depending on the route of administration and the nature of the immunizing tumor. Active I-RNA preparations were insensitive to treatment with deoxyribonuclease or pronase, but were inactivated by ribonuclease treatment; thereby indicating that the active moiety was one or more species of RNA. The active fractions of the I-RNA preparations had sedimentation values in sucrose density gradients of 12-16S, and comprised only a small fraction of the total RNA present in the lymphoid cells. Active antitumor I-RNA appeared to be localized in the cytoplasm of sensitized lymphoid cells, rather than in the nucleus. Lymphocytes from normal human donors as well as from cancer patients, when incubated with xenogeneic or allogeneic I-RNA, became specifically cytotoxic for human tumor cells in vitro. Crossreactivity among tumors of the same histologic type was observed, but not crossreactivity with tumors of other histologic types. Xenogeneic I-RNA extracted from the lymphoid organs of donor animals immunized either iwth tumor cells or normal tissues, following incubation with normal allogeneic lymphocytes, mediated cytotoxic immune reactions which were directed both against tumor-associated antigens and normal transplantation antigens. However, when autologous lymphocytes were used as effector cells, only immune reactions directed against tumor-associated antigens were observed. Allogeneic I-RNA extracted from peripheral blood lymphocytes of human cancer patients mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type. I-RNA's directed against "self" normal cell surface antigens appear to be recognized as self by lymphocytes, and immune responses against these self antigens are not elicited. On the other hand, I-RNA's directed against "nonself" tumor-associated antigens induce lymphocytes to effect specific antitumor immune responses. Our data are consistent with the hypothesis that I-RNA is an information-containing ribonucleic acid molecule capable of mediating immune reactions in vitro which are specific for the tumor-associated antigens of the tumor used to immunize the I-RNA donor.
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PMID:Mediation of immune responses to tumor antigens in vitro by immune RNA. 107 64

It has been demonstrated that cells killed by heat or irradiation have four times greater affinity for actinomycin D (AMD) than do viable tumor cells. By using a double labeling technique, we were able to show that, with increasing amounts of AMD bound in cells, the incorporation of RNA precursors is proportionally decreased. However, in the presence of nonviable cells or of native DNA, the AMD-induced inhibition of [3H]uridine incorporation is markedly reduced. This reduction does not occur if DNase is added to the system. The accumulation of dead cells in the tumor vicinity during the natural course of tumor growth or therapy must be taken into consideration in planning therapeutic regimens. We suggest that, in combined chemo- and radiotherapy, increased effectiveness of AMD may be obtained by its use prior to irradiation, thereby assuring its direct access to the tumor cells. The addition of DNase could eliminate or greatly diminish the dead cell competition for the drug.
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PMID:The effect of dead cells on the activity of actinomycin D against mouse sarcoma 180 ascites. 118 4

Primary tumors induced in newborn hamsters by simian adenovirus SA7 were investigated in transfection experiments. Infectious DNA-protein complexes were readily detected in both the supernatant and pellet fractions obtained by a modified Hirt extraction procedure; DEAE-dextran was required for infectivity to become manifest. Infectivity could be abolished by exposure to DNase, but it was unaffected by SA7-specific antiserum or RNase, and only partially inactivated by trypsin treatment. SA7 tumor cells serially passaged either in tissue culture or in hamsters yielded infectious DNA complexes much less frequently and appeared to evolve into nonyielder cell lines. When large numbers of cells were lysed, intact virus could be recovered from all the primary tumors and from some of the subcultured cell lines. There was a correlation between the persistence of complete virus and the presence of infectious DNA-protein complexes. When the tumor cells carried very small amounts of intact virus, infectious DNA complexes could still be detected; when virus could no longer be detected in the tumor cells, infectious DNA complexes could no longer be found. The results suggest that a portion of the infectious DNA moieties exists as viral DNA-protein complexes in the tumor cells.
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PMID:Demonstration of infectious DNA in transformed cells. III. Correlation of detection of infectious DNA-protein complexes with persistence of virus in simian adenovirus SA7-induced tumor cells. 118 47

Human CG is composed of two subunits, alpha and beta. In addition to its eutopic synthesis in normal and malignant trophoblasts, the hormone is produced ectopically by a variety of tumor cell lines of nonplacental origin. Regulation of the alpha CG gene in trophoblasts appears to differ from that in nontrophoblasts. To determine whether these differences are reflected in the chromatin structure at the alpha CG locus, DNase I-hypersensitive sites within this domain were mapped in human tumor cell lines that differentially express the gene. Two hypersensitive sites were detected in DNA from cell lines that produce the alpha-subunit. The latter includes trophoblastic (JAr and JEG-3 choriocarcinoma) and nontrophoblastic (HeLa cervical carcinoma and ChaGo bronchogenic carcinoma) tumor cell lines. The most prominent site (HS 1) was located approximately 100 base pairs upstream from the transcription start site. In trophoblasts, accessibility of HS 1 increased substantially upon induction of the gene by cAMP, likely reflecting alterations in DNA-protein interactions at the cAMP response element and/or tissue-specific enhancer. In nontrophoblasts, where alpha-subunit synthesis is enhanced by sodium butyrate but not by cAMP, neither butyrate nor cAMP altered the accessibility of HS 1. The HS 2 is comprised of multiple sites with weak to moderate DNase sensitivity located downstream at +1600 to +4000 in cell lines that produce alpha-subunit. Cell lines that do not express the alpha CG gene possess a distinct hypersensitive site (HS 3) within the first intron at about +600; these include 3A-Sub-E (SV40 transformed placenta), CBT (glioblastoma multiforme), and CaSki (cervical carcinoma). Cleavage by DNase at HS 1 and HS 2 is not evident in nuclei from cell lines that do not produce alpha-subunit. These results suggest that HS 1 and HS 3 are characteristic of active and inactive states of the alpha CG gene, respectively, and that the accessibility of HS 1 generally correlates with the level of expression.
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PMID:Deoxyribonuclease-hypersensitive sites in the glycoprotein hormone alpha-subunit gene from trophoblastic and nontrophoblastic human tumor cell lines: correlation with expression and effect of chemical inducers. 137 9

The production of extracellular matrix proteins is an important element of tumor formation, and alterations in matrix protein metabolism may be critical to the process of tumor metastasis. Abundant expression of type IV collagen, the major structural protein of the basement membrane, is characteristic of the Engelbreth-Holm-Swarm (EHS) mouse sarcoma. In the present study, we evaluated mechanisms of transcriptional regulation of type IV collagen genes by analysing nuclear factors that bind to the promoter region. Gel mobility-shift assays indicated that specific proteins from EHS tumor bound the promoter and generated several unique shift patterns. The specific sequences to which these proteins bound were determined using DNAase I protection assays. DNA-binding proteins protected two regions from DNAase I digestion. The first region was similar to a GC box, the binding site for the transcription factor Sp1. The other footprint was a 30-bp region that contained the novel sequence motif, 'CCCTCCC' present in several other extracellular matrix promoters. Nuclear extracts isolated from tissues that variably express type IV collagen bound to this protected sequence with distinctly different shift patterns. Furthermore, in highly expressing tissues, unlabeled oligonucleotides containing the 'CCCTCCC' motif effectively inhibited nuclear protein binding with the entire promoter. Thus, it is likely that a novel protein or protein complex binds to these sequences. Furthermore, these sequences appear to be unique to the genes that encode basement membrane proteins, suggesting a specific role in their regulation.
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PMID:A novel sequence in the type IV collagen promoter binds nuclear proteins from Engelbreth-Holm-Swarm tumor. 163 Aug 13

The DNA from a wide variety of human tumors has sustained mutations within the conserved p53 coding regions. We have purified wild-type and tumor-derived mutant p53 proteins expressed from baculovirus vectors and examined their interactions with SV40 DNA. Using DNAase I footprinting assays, we observed that both human and murine wild-type p53 proteins bind specifically to sequences adjacent to the late border of the viral replication origin. By contrast, mutant p53 proteins failed to bind specifically to these sequences. SV40 T antigen prevented wild-type p53 from interacting with this region. These data show that normal but not oncogenic forms of p53 are capable of sequence-specific interactions with viral DNA. Furthermore, they provide insights into the mechanisms by which viral proteins might regulate the control of viral growth and cell division.
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PMID:Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication. 164 78

Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of 'embryonic' type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron microscopy and time-lapse video-microscopy. Cells grown on type I collagen were stationary, showing a well-spread morphology and an extensive stress fibre pattern. Cells grown on type V collagen were also stationary, but displayed a poorly spread and elongated morphology. In contrast, cells grown on trimer collagen were motile and displayed a compact morphology and a reduced content of stress fibres. Both single-cell and group motility were detectable on trimer collagen substratum. These data are consistent with the existence of two opposite local signals, type I-trimer and type V collagens, which may confer a more or a less metastatic phenotype on breast carcinoma cells. Moreover, the synthesis of trimer collagen in d.i.c. is conceivably instrumental in providing new stromal pathways permitting tumour cells to infiltrate the host tissue.
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PMID:A comparison of spreading and motility behaviour of 8701-BC breast carcinoma cells on type I, I-trimer and type V collagen substrata. Evidence for a permissive effect of type I-trimer collagen on cell locomotion. 166 96

The activities of three human DNA metabolizing enzymes--uracil-DNA glycosylase, apurinic/apyrimidinic(AP)-DNA binding protein (an AP-DNA endonuclease) and the major cellular deoxyribonuclease (presumably DNase III and/or DNase IV)--were measured in logarithmic growing (diploid non-established) fibroblast strains, tumor-derived cell lines and SV40-transformed cell lines. The levels of activity of uracil-DNA glycosylase and DNase were increased, on average, 5- to 6-fold in tumor cell lines and 10-fold in SV40-transformed cell lines compared to those observed in normal fibroblast strains. AP-DNA binding activity was only 2- to 3-fold higher in both tumor-derived and SV40-transformed cell lines. Measurements in serum-deprived (and hence growth-retarded) SV40-transformed cells indicated that the observed increase in enzyme activity was only partially due to a higher proportion of S-phase cells in the rapidly growing transformed lines. Cell extract mixing experiments indicated that the relatively low levels of activity of the three enzymes in normal fibroblasts could not be ascribed to the presence of an inhibitory factor(s) in the crude extract.
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PMID:Increased uracil-DNA glycosylase, AP-DNA binding protein and deoxyribonuclease activities in tumor and SV40-transformed cell lines of human origin. 168 17

The aim of this study was to evaluate the variation in serum alkaline DNase activity (SADA) as a means of therapeutic monitoring in patients with head and neck cancer. Blood samples from 40 patients were collected before, during, and some weeks up to months after therapy. A decrease in SADA during treatment was usually associated with a primary clinical response, while no decrease indicated non-response to therapy. In patients with complete tumor regression the initial decrease of SADA was usually followed by an increase exceeding the initial level. A similar increase was not observed in patients with tumor progression.
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PMID:Predictive value of serum alkaline DNase activity variations in treatment of head and neck cancer. 169 27

The glycoprotein hormone alpha-subunit gene is expressed in a cell-specific manner in the anterior pituitary and placenta. Previous studies have shown that the region between -178 to -111 is indispensable for placental-specific expression of the human alpha-subunit gene. Using gene transfer techniques with chimeric luciferase plasmids, this report identifies regions of the mouse alpha-subunit promoter that are important for transcriptional activation in primary thyrotropic cells. Transient expression of a series of 5' flanking DNA deletions resulted in stepwise reductions of basal promoter activity between -480 to -417 (4-fold), -254 to -177 (5-fold), and -177 to -120 (3.5-fold). DNase-I protection analysis with nuclear extracts from thyrotropic tumor cells revealed specific protein-DNA interactions within each of these functionally defined regions. These were mapped to positions -474 to -452, -447 to -419, -213 to -170, and -158 to -101 within the 5' flanking region. In contrast, in mouse fibroblast L-cells no significant difference in alpha-subunit promoter activity was found by deleting the region from -480 to -177. However, a 3-fold decrease, similar to that found in primary thyrotropes, was found by deleting the region from -177 to -120. Further, a smaller region between -138 and -122 was the only area detected by the DNase-I protection assay using L-cell nuclear extracts. Thus, several cis-acting promoter elements located up-stream of position -177 are important for expression in thyrotropes. These elements also bind nuclear factors present in thyrotropes but not in nonpituitary fibroblasts and, therefore, differ from those mediating expression of the human alpha-subunit gene in the placenta.
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PMID:Identification of cis-acting promoter elements important for expression of the mouse glycoprotein hormone alpha-subunit gene in thyrotropes. 170 76


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