Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole derivatives to kynurenine. The inhibitory effect of interferon on many intracellular parasites such as Toxoplasma gondii and Chlamydia trachomatis is by the same mechanism. Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is induced in rodents after administration of interferon inducers, or influenza virus. IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the tumor rejection process. The gene for IDO has been cloned and shown to be differentially regulated by IFN-alpha and IFN-gamma. IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma. A possible role for IDO in O2-radical scavenging and in inflammation is discussed.
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PMID:Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. 175 66

A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP.
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PMID:[A case of renal pelvic squamous cell carcinoma accompanied with humoral hypercalcemia of malignancy]. 192 Oct 23

The proviral DNA of human T-lymphotropic virus type I (HTLV-I) was examined in 8 patients with adult T-cell leukemia/lymphoma (ATL/L) by Southern blot analysis. Judging from the number of bands containing viral DNA sequences in tumor cells, one and three copies of proviral genome were detected in 7 and 1 cases, respectively. The proviral genome in 1 case contained variant PstI sites and a single defective provirus which lost 5' LTR, gag and a part of pol genes was found in 2 cases. However, the pX region was detected in both of 2 latter cases by using the polymerase chain reaction. The results indicate that not all tumor cells from ATL/L yield infectious viruses and also support that the product of pX region may contribute to the tumorigenesis of HTLV-I.
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PMID:Human T-lymphotropic virus type I genome in adult T-cell leukemia/lymphoma. 193 71

The depletion of an essential amino acid (aa), tryptophan, caused by interferon-gamma (IFN-gamma)-mediated induction of indoleamine 2,3-dioxygenase (IDO) in mouse allografted tumor cells, has been suggested as a reason for the allograft rejection. To elucidate the mechanism of this IDO induction, attempts were made to isolate cDNA clones encoding mouse IDO. In seven of 25 mouse cell lines, IDO was induced by IFN-gamma, and the highest IDO induction was observed in the case of rectal cancer (CMT-93) cells, which were further stimulated two- to threefold by the simultaneous addition of dibutyryl cyclic AMP (Bt2cAMP). A cDNA library was prepared from poly(A)+ RNA isolated from CMT-93 cells treated with IFN-gamma/Bt2cAMP. The cDNA clones were isolated using the cDNA encoding human IDO as a probe. The mouse IDO cDNA encodes a 407-aa protein with an Mr of 45,639. The deduced aa sequence agreed with partial aa sequences derived from endopeptidase digestion of purified mouse IDO and revealed 61% homology with that of human IDO. Transient expression of the mouse IDO cDNA in COS-7 cells yielded a high level of IDO activity in the cells. Northern hybridization analysis of RNA in CMT-93 cells indicated that IFN-gamma induced the IDO mRNA, and that the level of RNA was increased by simultaneous addition of Bt2cAMP, while Bt2cAMP itself had no effect on mRNA induction.
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PMID:Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase. 193 18

A monomoprhic monoclonal antibody (LA45 antibody) reactive with "a new activation-induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek-Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha 1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha 1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others. Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin-activated T cells. We hypothesize the free heavy chains result from dissociation of beta 2-microglobulin from subpopulations of empty HLA-A,B molecules, or molecules with weakly bound peptides, that vary in size depending on cellular activation and peptide supply.
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PMID:Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells. 194 Jul 90

We report the cloning and characterization of a new ecotropic provirus encountered in a radio-induced thymic lymphoma of the C57BL/6 mouse. The provirus with an abnormally long LTR was inserted in the chromosomal DNA within the Pvt-1/MLVi-1/Mis-1 region which is a common integration site for MCF virus in mice and for Mo-MuLV in rats. This new ecotropic provirus was molecularly cloned and found to be infectious and competent for replication after transfection of murine cells. The recovered virus termed T3651/B was B-ecotropic, T-lymphotropic (in vivo) and highly leukemogenic for newborn C57BL/6 mice and for adult mice provided they were submitted to a subleukemogenic dose of irradiation. As compared to the AKV prototype N-ecotropic endogenous retrovirus, the T3651/B env proteins are only affected by few scattered point mutations. In contrast, the LTR has five repeats of enhancer sequences containing consensus motifs specific of the nuclear factors NF1-like, LVa, LVb and SEF1. Since a virus with such properties was encountered only once in 31 radio-induced tumors and isolated at a fourth tumor passage, a direct role of T3651/B virus in tumor genesis after irradiation is uncertain. Nevertheless, it is clear that T3651/B virus is a new leukemogenic retrovirus with a particular LTR structure which fits well with the model proposed by Rassart et al. (J. Virol. 58, 96-106, 1986) for the emergence of a thymotropic highly leukemogenic RadLV.
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PMID:A new leukemogenic retrovirus isolated from tumor cells derived from a radio-induced lymphoma of C57BL/6 mice: analysis of the env and LTR sequences. 204 96

The 2.9kb Sac I fragment (EJ2.9), which lacks the previously reported promoter/enhancers of the activated human c-H-ras-1, was used to study the interaction with the tumor virus promoter/enhancers or with the activated c-myc. When EJ2.9 constructs linked to the viral promoter/enhancers or to a viral enhancer even in the antisense orientation was transfected to the mouse cells, 16-39% of the foci induced with those linked in the sense orientation were formed. Further, the transforming activity decreased dramatically when the deletion was introduced from the upstream Sac I site to the 61 bases (-61) upstream of translational initiation codon, but the deletions to -144 did not significantly change the activity. Cotransfections with the activated c-myc were found also to enhance the transforming activity of EJ2.9 constructs either with or without the LTR linked in the antisense orientation. The transfected ras and myc were expressed as 1.2 and 2.5kb mRNAs, respectively, in each transformant. The in vitro mutagenesis suggested that the c-myc protein was involved in the enhancement. These results raise the possibility that the viral enhancers activate a cryptic promoter (s) within the region between -1 and -144 of p21 initiation codon by interacting with the region between -61 and -144 and that the c-myc protein also activates the same or different cryptic promoter(s) within the intron 0 or noncoding region of exon I, thus leading to the enhancement of the EJ2.9 transforming activity.
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PMID:[Enhancement of cellular transforming activities of truncated EJ c-H-ras-1 with viral enhancers or with c-myc]. 208 37

The depletion of an essential amino acid, tryptophan, caused by induction of indoleamine 2,3-dioxygenase (IDO), has been shown to be a mechanism involving self-defense against inhaled microorganisms and tumor growth. We recently reported that the IDO is dramatically (approximately 50-fold) induced in allografted tumor (3-methylcholanthrene-induced ascites type tumor cells) cells undergoing rejection, and that the enzyme is induced by factor(s) released through the interaction of allografted tumor cells with infiltrating leukocytes. The culture supernatant of infiltrating leukocytes, which were harvested on day 7 after tumor transplantation, induced the highest IDO activity in the tumor cells. The inducer activity was completely neutralized by the addition of antibody to IFN-gamma but not by antibody to IFN-alpha/beta. Approximately 6 U/ml of IFN-gamma was detected by an ELISA assay in the 12-h culture supernatant with 2 x 10(6) leukocytes/ml, and rIFN-gamma at 6 U/ml induced IDO in 3-methylcholanthrene-induced ascites type tumor cells to the same extent as IFN-gamma in the culture supernatant. Moreover, i.p. administration of antibody to IFN-gamma almost completely inhibited the induction of IDO in the allografted tumor cells. These observations indicate that the factor responsible for IDO induction in the allografted tumor cells is IFN-gamma.
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PMID:IFN-gamma is the inducer of indoleamine 2,3-dioxygenase in allografted tumor cells undergoing rejection. 211 80

Retrovirus vectors only integrate into the genome of dividing cells and can thus be used to selectively infect tumor cells in the adult rat brain. Gene delivery was assessed by using the retrovirus BAG vector, which bears the Escherichia coli lacZ gene under the MoMLV LTR promoter-enhancer element, and by histochemical staining for bacterial beta-galactosidase activity. Direct injection of this vector (90-900 cfu) into the adult rat brain, with or without prior inoculation of C6 glioma cells (2 x 10(5) cells) resulted in labeling of only a few cells as assessed 1 week later. When the psi 2-BAG packaging line was grafted into the brain, labeled psi 2-BAG cells could be found after 1 day, but not after 5 days, following grafting, suggesting that the grafted cells had been rejected and that no endogenous cells had integrated released vector, or that expression of lacZ had been turned off. In contrast, when the psi 2-BAG packaging line was grafted into a brain region, which had been inoculated previously with rat C6 glioma cells (2 x 10(5) cells), beta-galactosidase labeling of these tumor cells, identified by immunocytochemistry for glial fibrillary acidic protein and S100, could be demonstrated 10 days later. Thus, grafting of retrovirus packaging lines into adult brain provides a mean to infect tumor cells in situ. The grafted packaging cells may continue to release retrovirus particles for an extended period, thus infecting more cells at the stage of division appropriate for viral integration, as compared to inoculation of the virus alone. Grafting of retrovirus packaging cell lines could be used to selectively deliver "killer" or "suppressor" genes to tumor cells in the brain to curtail their growth.
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PMID:Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line. 212 47

The LTR, v-src, LTR provirus, which arose by the reverse transcription and integration of src mRNA in the H-19 hamster tumor, has been successfully rescued by fusion with chicken fibroblasts infected with Rous-associated virus RAV-1. One rescued virus, E6, acquired 1 kilobase of the 5' end of the gag gene structure. Recombination took place in the region of 15-nucleotide homology exactly between v-src exon (position 7054) and gag (position 1417). This recombination resulted in the alteration of src splice acceptor site sequences, but this site is maintained as a functional splice acceptor site. The nucleotide structure of the long terminal repeat of recombinant E6 virus suggests that it arose by the intermolecular jump of reverse transcription from RAV-1 to src mRNA and then the switch of templates between already depicted regions of homology. The second jump of reverse transcription was apparently an intramolecular event. The acquisition of 1 kilobase of the 5' gag by E6 resulted in maintaining the balance of unspliced and spliced E6 RNAs and assured the replication advantage of rescued E6 virus over rescued F6 virus, the genome of which corresponds to that present in ancestral H-19 cells.
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PMID:A transformation-competent recombinant between v-src and Rous-associated virus RAV-1. 215 71


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