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)

The human ETS2 and ERG genes are members of the ETS gene family, with sequence homology to the viral ets gene of the avian erythroblastosis retrovirus, E26. These genes are located on chromosome 21 and molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 suggested that ETS2 may be a gene within the minimal DS genetic region. We have, in fact, been able to confirm the presence of the ETS2 gene dosage in triplicate occurring in occult human 21 chromosome abnormalities. It is known that ERG and ETS2 gene translocations occur in certain specific leukemias associated with defined chromosome rearrangements [e.g., t(8;21)]. Moreover, it is known that DS individuals are at greater risk for leukemic disease than their normal familial cohorts, implying that trisomy of that region of human chromosome 21 may play a role in the development of this type of neoplasia. The human ETS genes, first identified in our laboratory, are highly conserved, being found from lower organisms, like Drosophila and sea urchin, to humans. In mammals, the ETS genes are structurally distinct, located on separate chromosomes; they are transcriptionally active and differentially regulated. The ETS2 protein is phosphorylated and turns over with a half-life of approximately 20 min. After activation with the tumor promoter, TPA, the level of ETS2 elevates 5- to 20-fold. The properties of the ETS2 protein, such as nuclear localization, phosphorylation, rapid turnover, and response to protein kinase C, indicate that this protein belongs to a group of oncogene proteins thought to have regulatory functions in the nucleus. In the mouse thymus ets-1 and ets-2 are 8-10-fold higher, respectively, in the CD4+ subset than in other subsets examined, suggesting a role in T-cell development for these genes. Cells transfected with the cellular ets-2 gene, expressing higher levels of ets-2 products, showed a stimulated proliferation response, abolished their serum requirement and formed colonies in soft agar that could induce tumors in nude mice. Collectively, these data suggest that this family of genes might play a role in controlling specific steps of the signaling transduction pathway. Thus, the ETS genes, as other genes with homology to viral oncogenes, might be instrumental in regulating cellular growth and differentiation, as well as organismal development.
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PMID:ETS family of genes in leukemia and Down syndrome. 214 58

The diagnostic accuracy of serum thyroglobulin (S-TG) determination as measured under endogenous thyrotropin(TSH)stimulation (ETS) has been investigated in 372 patients with completed therapy for differentiated thyroid cancer. In 51 of these (13.7%) S-TG could be detected by means of the IRMA-technique. In 34 S-TG determination was additionally performed during suppressive thyroxine therapy (SSH): S-TG in SSH was significantly lower as compared with S-TG in ETS (p less than 0.001). In seven cases with proven metastases S-TG values were pushed below the minimal detection level by SSH. Tumor manifestations with suppressible S-TG were significantly smaller (mean = 5 ccm, range 1-25 ccm) than those with non-suppressible S-TG (mean = 90 ccm, range 11-125 ccm, p less than 0.005) and displayed a papillary histology. There was a moderate correlation between S-TG concentration and tumor volume (r = 0.71; p less than 0.001). 21% (n = 66) of patients with undetectable S-TG in ETS showed 131I-uptake in the thyroid region; 2% (n = 7) had proven metastases. Sensitivity of S-TG determination for the detection of metastases amounted to 82.5% in ETS and 53.3% in SST, specificity was 94.6% in ETS and 99.7% in SST. It is concluded that small metastases of papillary thyroid carcinomas may escape S-TG screening more readily than follicular carcinoma metastases when S-TG concentrations are measured during thyroxine treatment.
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PMID:[Serum thyroglobulin in the diagnosis of metastases of differentiated thyroid cancer. Effect of suppressive thyroid hormone substitution on the diagnostic accuracy of thyroglobulin values]. 379 59

Wist: Han/Pce SPF strain rats were administered dimethylnitrosamine (DMNA) in 0.04% concentration since the first day after birth. Total dose of 0.2 mg per infant rat was administered on 1st to 5th day of life, 0.4 mg/infant rat on 1st to 10th day and 0.5 mg on 1st to 20th day of life. Maximum survival time was one year. Both higher DMNA doses were already toxic the effect manifesting itself by increased mortality of the infant rats (liver hemorrhages, bleeding into the intestinal lumen) and reduced weight increment. Hepatic and renal tumors were detected in the rats beginning with their 19th week of life. In the liver they were hepatocellular carcinomas, to a lesser extent also cholangiomas and cavernomas. Further, increased incidence of preneoplastic nodular hyperplasia and benign hepatomas was demonstrated. In the kidney it was always the case of mixed mesenchymal tumor. Comparison of the results of postnatal study with a long-term carcinogenic DMNA study is discussed and possible reasons of different localization and characteristics of tumors dependent on DMNA administered were demonstrated.
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PMID:Postnatal carcinogenic study of dimethylnitrosamine in rats. 398 62

The relationship between topoisomerase II activity and ribosomal RNA synthesis was investigated using the antitumoral drug VM26, a specific inhibitor of topoisomerase II. For this purpose TG cells, a human tumor cell line, were cultured in the presence of 2.5 microM VM26 for 1 and 3 h; VM26 reduced the topoisomerase II activity, measured in whole cell extracts. In the presence of VM26 the [3H]uridine incorporation into ribosomal RNA was decreased; electron microscopy investigation of nucleoli showed a segregation of nucleolar components. Because VM26 stabilizes the cleavable complex and inhibits the resealing reaction, thus causing potential cleavage sites, we have analyzed the double-strand breaks caused by the drug treatment in the tandem repeat ribosomal DNA (rDNA) genes, by indirect labeling with two probes recognizing the 5' portion of ETS (BES) and the 3' portion of 28S (LS6BE) transcribed gene. In VM26-treated cells rDNA is fragmented and a topoisomerase II preferential cleavage site is present, localized at 1.85 kb in 28S region from 3' EcoRI site.
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PMID:Inhibition of topoisomerase II activity and its effect on nucleolar structure and function. 751 Feb 50

Translocations in bands 11q23.3-11q24 are associated with several human cancers, including acute lymphoid and acute myeloid leukemias (AML) and Ewing's sarcoma. We have characterized two independent deletions in this region, one derived from a patient with AML who previously had a T-cell lymphoma, and another from a Wilms' tumor patient. Cytogenetic analysis of the ML-2 cell line established from the malignant cells of the AML patient indicated that one chromosome 11 homolog had an interstitial deletion, del(11) (q23q24), and the remaining homolog was involved in a recurring translocation, t(6;11) (q27;q23). According to karyotype analysis on the Wilms' tumor patient (EH), one chromosome 11 was normal and the other carried an interstitial deletion at 11q23.3-11q25. Somatic cell hybrids segregating the EH deletion (EHR4) and the ML-2 deletion (MLR4) have been isolated. The EH deletion is distal to the MLL probe recently associated with 11q23.3 leukemia breakpoints (Ziemin-van der Poel et al.: Proc Natl Acad Sci USA 88:10735-10739, 1991). The ML-2 deletion could involve the MLL gene at a point distal to other breakpoints within MLL. Both deletions include the Ewing's sarcoma breakpoint at 11q24.1. By Southern blot analysis we identified three anonymous DNA markers (D11S272, D11S273, and D11S219) and the ETS/oncogene, which map within each deleted region. These markers are conserved based on zoo blot analysis, and they are valuable for physical mapping and genetic characterization of a region that may code for gene products associated with growth control and tumor suppression in a variety of cancers.
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PMID:Characterization of two 11q23.3-11q24 deletions and mapping of associated anonymous DNA markers. 768 55

Most Ewing's sarcomas or related primitive neuroectodermal tumors have the (11;22)(q24;q12) or less frequently the (21;22)(q22;q12) translocation. These rearrangements fuse the EWS gene on chromosome 22q12 to either the FLI1 or ERG genes, both members of the ETS family of transcription factors. Simple variant chromosomal translocations have been occasionally described in these tumors. We have identified a third Ewing's sarcoma translocation, the t(7;22)(p22;q12), that fuses EWS to the human homologue of the murine ETS gene ER81. This gene, designated ETV1 (for ETS Translocation Variant), is located on chromosome band 7p22. Identical EWS nucleotide sequences found in the majority of EWS-FLI1 and EWS-ERG chimeric transcripts are fused to a portion of ETV1 encoding an ETS domain with sequence specific DNA-binding activity. These findings confirm that the fusion of EWS to different ETS family members can result in a similar tumor phenotype.
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PMID:A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. 770 Jun 48

TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13. In some cases, both TEL alleles are affected, resulting in loss of wild-type TEL function in the leukemic cells. In addition, 5% of children with acute lymphoblastic leukemia (ALL) have 12p12-p13 deletions, suggesting that a tumor suppressor gene resides on 12p. These observations led us to consider whether TEL loss of function may contribute to the pathogenesis of ALL. In this report we show that the TEL gene maps between the polymorphic markers D12S89 and D12S98, and we use these flanking markers to screen paired diagnosis and remission samples from 81 children with ALL for loss of heterozygosity (LOH) at the TEL gene locus. Fifteen percent of informative patients showed TEL LOH which was not evident on cytogenetic analysis. Detailed examination of patients with LOH at this locus showed that the critically deleted region included two candidate tumor suppressor genes: TEL and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. These studies show that LOH at the TEL locus is a frequent finding in childhood ALL.
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PMID:Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood. 779 47

We have determined the frequency of EWS fusion transcripts in a series of primary Ewing's sarcomas and peripheral primitive neuroectodermal tumors and cells lines. Type 1 and 2 EWS-Fli1 fusions were demonstrated in 8 cell lines and 14 patient samples. Five patients with cytogenetically characterized rearrangements of chromosome 22 that did not involve chromosome 11 were included in these studies. A novel EWS-Fli1 in-frame isoform fusing EWS to exon 8 of Fli1 was isolated from a tumor with a variant t(12;22;22)(q14;p1;q12) translocation. Three in-frame isoforms of a novel hybrid transcript derived from the fusion of EWS with the ETS domain of the human erg gene were identified in patient samples and a cell line with cytogenetically unidentified or cryptic translocations involving chromosomes 21 and 22. Interphase analysis by fluorescent in situ suppression hybridization using two overlapping erg yeast artificial chromosome clones demonstrated disruption of the erg gene on chromosome 21 in a patient sample with monosomy 22. Our results provide new information about the involvement of EWS in small round cell tumors involving exchange of its putative RNA-binding domain with DNA-binding domains derived from different members of the ETS family of transcription factors. These studies emphasize the utility of reverse transcriptase PCR analysis and fluorescent in situ hybridization as additional diagnostic tools for differential diagnosis among small round cell tumors.
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PMID:EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations. 804 Mar 1

Erythro-alkane-6,8-diols were isolated from the flowers of Carthamus tinctorius. 12-0-Tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, was applied to the ears of mice to induce inflammation. Of 8 alkane-6,8-diols assayed, the C27, C31, C32, C33 and C35 alkane diols inhibited the inflammation. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.5-0.7 mg/ear. However, C21, C23 and C25 alkane-6,8-diols were found to have no effect. Furthermore, the mixture of erythro-alkane-6,8-diols from the flowers of C. tinctorius markedly suppressed the promoting effect of TPA on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene.
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PMID:Inhibitory effect of alkane-6,8-diols, the components of safflower, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. 860 39

We have shown previously that loss of heterozygosity at chromosome band 12p13 is among the most frequent genetic abnormalities identified in acute lymphoblastic leukemia (ALL) of childhood. Two known genes map within the critically deleted region of 12p: TEL, the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. Both genes are, therefore, excellent candidate tumor suppressor genes. In this report, we determined the exon organization of the TEL gene and performed mutational analysis of TEL and KIP1 in 33 childhood ALL patients known to have loss of heterozygosity at this locus. No mutations in either TEL or KIP1 were found; this suggest that neither TEL nor KIP1 is the critical 12p tumor suppressor gene in childhood ALL.
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PMID:Mutational analysis of the candidate tumor suppressor genes TEL and KIP1 in childhood acute lymphoblastic leukemia. 864 Aug 33


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