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

The isolated laminin receptor (LN-R) labeled by 125I was reconstituted into liposomes. 125I-LN-R-liposomes and free 125I-LN-R were separated by Sepharose 4B column chromatography. The LN-R-liposomes showed affinity for laminin (LN) and were capable of binding to immobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes were fused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol (PEG) induction. The radiation with the fused cells was not removed by salt solution. The binding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%. Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-R were injected into C57BL/6J mice through tail veins (5 x 10(5) cells/each mouse) respectively. The mice in the test group died earlier than those in the control group. The total weight of lung tumor in the test group remarkably increased in comparison with those in the control group. The results taken together directly demonstrated that LN-R on carcinoma cell surface were involved in the recognition and binding of the cancer cells to LN in basement membranes, and also LN-R was of a crucial biological molecule in cancer metastasis.
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PMID:Studies on transplantation of the laminin receptor and its roles in experimental metastasis of murine Lewis lung carcinoma cells. 130 46

Severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from Epstein-Barr virus (EBV) negative human donors develop aggressive tumors after the chimeric mice are infected with EBV. The tumors were composed of human B cells that expressed EBV encoded antigens (latent membrane protein and EBV nuclear antigen2). Southern blot analysis of DNA from 16 SCID/hu tumors with human Ig gene probes showed that each tumor contained multiple heavy and light chain gene rearrangements. Ig kappa gene rearrangements were frequent, while clonal lambda gene rearrangements were infrequent. Analysis of EBV terminal repeat sequences indicated two or more fused termini in each tumor, consistent with a multiclonal origin. Linear terminal repeat segments and viral antigens (EA-D and EA-R) associated with EBV replication were not detected in the tumors. High levels of human Igs in the SCID/hu serum were oligoclonal and primarily contained kappa light chains. Before the appearance of overt tumors, circulating cells with human and EBV DNA could be detected in the SCID/hu mice by the polymerase chain reaction. We conclude that EBV infection in SCID/hu chimeric mice produces a limited number of transformation events, which give rise to oligoclonal tumors resembling EBV-associated lymphoproliferative disorders in some immune-deficient patients.
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PMID:Epstein-Barr virus induced lymphoproliferative tumors in severe combined immunodeficient mice are oligoclonal. 130 25

Histological and anatomopathological studies performed on 152 independent myeloblastosis-associated virus type 1 (MAV1)-induced nephroblastomas allowed us to precisely define the chronology of tumor development in chickens. Three tumors representing increasing developmental stages were used to construct genomic libraries and to study both the state of proviral genomes and the sites of MAV1 integration in genomic DNA. We established that increasing levels of proviral rearrangement, eventually leading to the elimination of infectious MAV genomes, were associated with tumor progression and that 22 individual tumors, representative of different developmental stages, did not contain any common MAV1 integration site. Cloning of cellular fragments flanking the MAV1-related proviruses in tumor DNA showed that each one of eight nephroblastomas tested expressed a high level of an as yet unidentified cellular gene (nov) whose transcription is normally arrested in adult kidney cells. Cloning of the normal nov gene established that in one tumor, fused long terminal repeat-truncated nov mRNA species were expressed, indicating that at least in that case, the high level of nov expression was under the control of the MAV long terminal repeat promoter. The normal nov gene encodes a putative 32-kDa secreted polypeptide, which is a member of a new family of proteins likely to be involved in cell growth regulation. We also showed that the expression of an amino-terminal-truncated nov product in chicken embryo fibroblasts was sufficient to induce their transformation.
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PMID:Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. 130 86

Monocytes and macrophages express the receptor for the hematopoietic growth factor colony-stimulating factor 1 (CSF-1) and require this factor for growth in culture. A murine monocyte tumor cell line that lacks the usual requirement for CSF-1 was isolated. On the basis of the similarity of the structures of the CSF-1 and platelet-derived growth factor (PDGF) receptors and because monocytes normally secrete PDGF, we analyzed the tumor cell line for anomalous expression of the PDGF-R beta gene. Two different cDNAs that each contain sequences corresponding to the complete coding sequence of PDGF-R beta fused (in frame) to the amino-terminal half of the CSF-1 receptor were isolated. Introduction of these PDGF-R beta-related cDNAs into two partially transformed, CSF-1-dependent monocyte cell lines resulted in autonomous growth and cell transformation. These monocyte cell lines exhibit a novel form of growth factor receptor activation that can lead to oncogenic growth in collaboration with the c-myc oncogene.
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PMID:A colony-stimulating factor 1 (CSF-1) receptor/platelet-derived growth factor-beta receptor gene fusion confers CSF-1 independence and tumorigenicity on a c-myc-immortalized monocyte cell line. 130 94

Expression of the viral oncogene encoding the simian virus 40 (SV40) large tumor antigen (T antigen) typically promotes tumorigenesis in mammalian cells. To generate transgenic mice that express T antigen in rod photoreceptors, a chimeric construct consisting of a mouse opsin promoter fragment fused to the coding region of SV40 T antigen was generated. Expression of T antigen in the transgenic retina began at early stages of postnatal development concomitant with expression of endogenous opsin. Instead of inducing hyperplasia or tumor formation, T-antigen expression caused a rapidly progressing photoreceptor degeneration. The degeneration was accompanied by sustained DNA synthesis in photoreceptor cells, as evidenced by incorporation of [3H]thymidine and by the appearance of mitotic figures at postnatal day 10, a stage when nontransgenic photoreceptor cells are postmitotic and quiescent. Although transgenic photoreceptor cells undergo S phase and enter mitosis, the consequences of T-antigen expression are not proliferation and tumorigenesis but proliferation and cell death.
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PMID:Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. 131 Oct 85

Transgenic mice for the promoter sequence of bovine arginine vasopressin (AVP) gene fused to large SV40 T-antigen coding sequence develop pituitary tumors and insulin-producing pancreatic tumors. In order to establish the cellular composition of the pituitary tumors, histological, immunocytochemical, in situ hybridization, and electron microscopic technics were applied. Pituitary anterior lobe tumors were identified in 10 out of 14 glands examined. In 2 of these cases, intermediate lobe tumors were also found. The anterior lobe tumors contained a variable number of GH immunoreactive cells. In situ hybridization performed in 7 cases revealed a diffuse distribution of GH messenger RNA over all tumor cells. Ultrastructurally, the tumors contained undifferentiated cells with very small secretory granules and rare cells showing some resemblance to somatotrophs. The results indicate that these pituitary tumors are composed of undifferentiated somatotrophs. The presence of a few PRL immunoreactive cells in four tumors and scattered TSH immunoreactive cells in two tumors supports the view that somatotrophs have the potential to produce PRL and TSH. The intermediate lobe tumors were immunoreactive for ACTH and intensely positive for POMC mRNA. In the nontumorous adenohypophyses, no hyperplasia of any cell type was noted. Several GH immunoreactive cells exhibited pleomorphic, giant nuclei and mitoses. In conclusion, the majority of transgenic mice for AVP/large T-antigen develop pituitary tumors originating in and composed of somatotrophs. Less frequently, intermediary lobe tumors were present as well. AVP/SV40 transgenic mice provide a unique experimental model for somatotroph tumors that are neither preceded by, nor associated with somatotroph hyperplasia.
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PMID:Morphology of adenohypophysial tumors in mice transgenic for vasopressin-SV40 hybrid oncogene. 131 26

Epstein-Barr virus (EBV) is known to be associated with two human malignant diseases, nasopharyngeal carcinoma (NPC) and endemic Burkitt's lymphoma. In this study, the genotypes of EBV in tissues from 13 NPC patients in Japan were analyzed by Southern blot hybridization using EBV genome fragment probes. Ten of the cases contained reiterated sequences (EBV BamHI-H, -B1*, -K fragments), showing that only one genotype was detected in each specimen. One of these had a BamHI fragment containing a fused sequence of BamHI-Y and -H. In all except one case, a single-sized EBV-joined terminus was observed in each NPC specimen, implying evolution of the carcinoma from a single EBV-infected cell. One metastatic lymph node (which was not a primary epipharyngeal tumor) contained EBV with heterogeneous termini suggesting production of linear virion DNA. The type C variant resulting from loss of a BamHI site between the BamHI-W1* and -I1* regions was observed in 7 of the 10 cases, and the other 3 cases had a separated BamHI-I1* fragment. As reported by Lung et al. (Virology, 177: 44-53, 1990), the type C variant appears to be dominant among Japanese strains, as it is in Southern China. In contrast to their findings, however, the "f" variant with an extra BamHI site in the BamHI-F region which they found to be strongly associated with NPC specimens from Southern China, was detected in only one case. The present study, therefore, did not support the specific association of the "f" variant with NPC in Japanese patients. We conclude that the EBV in NPC tissues exists in variants. Further studies along these lines, could help to explain the epidemiology of EBV.
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PMID:[A basic study on the association of Epstein-Barr virus with nasopharyngeal carcinoma--detection and genotypic analysis of Epstein-Barr virus associated with nasopharyngeal carcinoma in Japanese patients]. 132 Jan 17

The biosynthesis in Leydig cells of the C19 steroid testosterone from the C21 precursor progesterone requires the activities of the enzyme cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P450(17 alpha)). Previous studies from this laboratory demonstrated that the de novo synthesis of the P450(17 alpha) protein and the accumulation of P450(17 alpha) mRNA in mouse Leydig cell cultures is absolutely dependent on cAMP stimulation. To investigate further the cAMP regulation of P450(17 alpha) expression in Leydig cells, the structural gene encoding P450(17 alpha) (Cyp17) was isolated from a mouse genomic library using a full-length mouse P450(17 alpha) cDNA. Two overlapping genomic clones were isolated and characterized by restriction mapping and partial sequencing. The two clones together contain the entire coding region and approximately 10 kilobases of 5'-flanking sequences of Cyp17. To identify regions necessary for cAMP-induced transcription, 5'-flanking regions of Cyp17 were fused with the chloramphenicol acetyltransferase (CAT) reporter gene and transiently transfected into MA-10 tumor Leydig cells. Studies localized the cAMP-responsive region of the gene to a region between -346 and -245 basepairs relative to the transcription initiation site. Transient transfections of MA-10 cells with a construct consisting of the -346/-245 sequences fused to a heterologous promoter, thymidine kinase, and the CAT reporter gene demonstrated a marked increase in cAMP stimulation of CAT expression, providing additional evidence that the -346/-245 sequences of the Cyp17 5'-flanking region confer cAMP-induced expression of Cyp17. This cAMP-responsive region of mouse Cyp17 bears no apparent homology to the cAMP-responsive regions identified in the human and bovine Cyp17 genes.
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PMID:Isolation and characterization of the mouse P450 17 alpha-hydroxylase/C17-20-lyase gene (Cyp17): transcriptional regulation of the gene by cyclic adenosine 3',5'-monophosphate in MA-10 Leydig cells. 132 57

Terminal differentiation of skeletal muscle cells is obligatorily accompanied by the expression of a battery of muscle-specific genes and cell fusion to form multinucleated myotubes. The transcription of some of the muscle-specific genes is activated by the products of myoD gene family including MyoD and myogenin. The mouse skeletal muscle cell line C2SVTts11, which is a clone of C2 cells transfected with SV40 T antigen genes (temperature-sensitive large T and wild-type small t) fused to metallothionein gene promoter, is prevented from differentiation when the large T is induced. If the large T is induced in the myotubes, which are preformed in the absence of large T expression, the terminally differentiated cells reenter the cell cycle. In good accordance with the induction of large T, endogenous c-jun but not c-fos or c-myc mRNA was induced, whereas the expression of myoD and myogenin was suppressed. Treatment of quiescent C2 cells with a tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, transiently induced c-jun and c-fos mRNAs, and temporarily deinduced myoD and myogenin mRNAs just after the expression of the protooncogenes. To ascertain whether c-jun induced by large T is sufficient to inhibit myogenic differentiation, c-jun cDNA was transfected into C2 cells. As the levels of exogenous c-jun expression were higher in the transfected clones, the cells expressed lower levels of myoD gene family and they formed fewer myotubes. Even the cells expressing the highest levels of exogenous c-jun, however, still formed small myotubes containing a few nuclei under differentiation conditions. These results suggest that large T inhibits myogenic differentiation by suppressing the expression of the members of myoD gene family, partly through inducing c-jun. In addition to this, other mechanisms seem to be required to achieve complete inhibition.
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PMID:SV40 large T inhibits myogenic differentiation partially through inducing c-jun. 133 Oct 38

Many proteins produced in Escherichia coli accumulate in inclusion bodies. We have systematically evaluated the parameters that affect the refolding and renaturation of enzymatically active molecules from bacterial inclusion bodies containing a recombinant single-chain immunotoxin, B3(Fv)-PE38KDEL. This recombinant molecule is composed of the variable domains of monoclonal antibody B3 (B3(Fv)) fused to a truncated mutant form of Pseudomonas exotoxin A (PE38KDEL). This immunotoxin kills carcinoma cells in vitro, causes tumor regression in animal tumor models, and is being developed as an anti-cancer therapeutic agent (Brinkmann et al., 1991, Proc. Natl. Acad. Sci. USA 88, 8616-8620). Like many other recombinant proteins, B3(Fv)-PE38KDEL is produced in E. coli in inclusion bodies and must be denatured and refolded to become active. This requires correct folding, formation of native disulfide bonds, and the association of different domains. All these steps are strongly dependent on the renaturation conditions used. Optimum conditions of refolding were obtained by the addition of reduced and oxidized thiol reagents to promote disulfide bond formation and the addition of a labilizing agent such as L-arginine. Furthermore, the necessity to reactivate proteins at low protein concentrations due to its tendency to aggregate at high concentrations was overcome by a step-by-step addition of denatured and reduced protein into the refolding solution. This approach should be useful for the production of active forms of other recombinant proteins.
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PMID:A method for increasing the yield of properly folded recombinant fusion proteins: single-chain immunotoxins from renaturation of bacterial inclusion bodies. 133 41


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