Disease relevance of TBXAS1

• Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer [1].
• Here, we compared the expression levels of thromboxane synthase (TXS), which catalyzes the conversion of PGH(2) to thromboxane A(2) (TXA(2)), between human colorectal cancer tissue and its accompanying normal mucosa [2].
• TXS was also highly expressed in human colonic cancer cell lines [2].
• In summary, TBXAS appears to be one of the up-regulated downstream enzymes of Cox metabolism in pituitary tumors [3].
• Pituitary adenomas and carcinomas also showed greater staining for TBXAS when compared to normal pituitary [3].

Psychiatry related information on TBXAS1

• The aim of the present investigation was to study the effect of an experimental stressor on mRNA levels in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for cell division, while investigating possible individual differences in stress reactivity [4].

High impact information on TBXAS1

• Thymidylate synthase (TS, EC 2.1.1.45) catalyzes the reductive methylation of dUMP by CH2H4folate to produce dTMP and H2folate [5].
• CONCLUSIONS AND IMPLICATIONS: Characterization of tumor TS expression may be of value in identifying patients with advanced head and neck cancer who would benefit from fluoropyrimidine-based neoadjuvant chemotherapy [6].
• Our results show that virulent Leishmania require at least one copy of dhfr-ts and argue that DHFR-TS plays an unanticipated role in addition to its role in the de novo synthesis of thymidine [7].
• With either of these agents the SW620 line required higher drug concentrations or longer incubation times than HT29 cells to achieve a given level of fragmentation or cytotoxicity, even though the two cell lines are equally sensitive to FdUrd-induced TS inhibition [8].
• HT29 and SW620 cells yielded similar fragment size distributions upon treatment with either FdUrd or CB3717 [a folate analog inhibitor of thymidylate synthase (TS)] [8].

Chemical compound and disease context of TBXAS1

• In the subgroup of patients treated with surgery alone, the expression of TS in lymph node metastases also had a prognostic value for OS (P = .04) and DFS (P = .03), but this was not the case for the other subgroup who received adjuvant fluorouracil-based chemotherapy (OS, P = .5; DFS, P = .2) [9].
• PURPOSE: To compare raltitrexed (Tomudex; Zeneca Pharmaceuticals Ltd, Macclesfield, United Kingdom) a direct, specific thymidylate synthase (TS) inhibitor with fluorouracil (5-FU) plus high-dose leucovorin (LV) as first-line treatment for advanced colorectal cancer (ACC) [10].
• We have correlated TS protein and gene expression with the response in patients with colorectal (n = 9) and gastric cancer (n = 12) treated with infusional 5-FU plus leucovorin (LV) or infusional 5-FU/LV and cisplatin, respectively [11].
• The goal of this study was to improve the therapeutic index of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) system by the addition of thymidylate synthase (TS) inhibitors [12].
• We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy [13].

Biological context of TBXAS1

• Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization [14].
• The gene encoding human thromboxane synthase (TBXAS1) was isolated from a human EMBL3 genomic library using human platelet thromboxane synthase cDNA as a probe [15].
• Gene expressions of PGS and TXS were significantly induced after 6 h of high pressure perfusion [16].
• Thromboxane synthase (TBXAS1), a cytochrome P450 enzyme, converts prostaglandin H2 into thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation [17].
• Twelve coding-region variants were identified in the human TBXAS1 gene in 48 African-American and 46 Caucasian individuals, of which eight were amino-acid substitutions [17].

Anatomical context of TBXAS1

• Differential expression of thromboxane A synthase and prostaglandin H synthase in megakaryocytic cell line [18].
• We determined the expression of isoforms of prostaglandin H synthase (PGHS) and thromboxane A synthase (TXAS) in a human megakaryocyte cell line (MEG-01 [18].
• RESULTS: The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells [19].
• By sequence alignment, the first 6 residues of the mature TXS polypeptide are likely to form a distinctive "tail" structure not found in many other mammalian cytochromes P450 in the endoplasmic reticulum membrane [20].
• It is proposed that different kinetics of PGE synthase and TXA synthase account for the patterns of production of these eicosanoids in monocytes under a variety of experimental conditions [21].

Associations of TBXAS1 with chemical compounds

• Characterization of the human gene (TBXAS1) encoding thromboxane synthase [15].
• Analysis of arachidonate metabolism in cells induced by PMA for 3 and 5 days showed a high level of PGH2 synthesis which exceeded the TXAS capacity for TXA2 synthesis [18].
• Despite a high TXAS level, uninduced MEG-01 cells synthesized only a small amount of thromboxane A2 (TXA2) due to limited PGHS-1 or PGHS-2 expressions [18].
• Peptides with either the ultimate 10 or 15 residues of the NH2 terminus of TXS were synthesized and used to produce site-directed antibodies [20].
• Also, TXA synthase was saturated at lower substrate concentrations than PGE synthase [21].

Physical interactions of TBXAS1

• Furthermore, chromatin immunoprecipitation assay using the stably transfected A549 cells demonstrated that Nrf2 bound the TXAS NF-E2 site in vivo [22].
• Band shifting and chromatin immunoprecipitation assays indicated that p45 NF-E2 was bound to the TXAS promoter in vitro and in vivo [23].

Regulatory relationships of TBXAS1

• We previously showed that p45 NF-E2 activated the TXAS promoter in hematopoietic cells via binding to the nucleotides -86/-77 from the transcriptional start site [Yaekashiwa and Wang (2002) J. Biol. Chem. 277, 22497-22508] [22].

Other interactions of TBXAS1

• We conclude that TXAS and PGHS are differentially expressed in MEG-01 during PMA-induced differentiation [18].
• Only traces of PGHS-2 mRNA and alternate-spliced TXAS mRNA were detected in human platelets [18].
• A similar differential expression pattern was seen in tumours from patients with different prognosis, in that patients with predicted poor prognosis had higher, but not statistically different, levels of TBXA2R, and significantly lower levels of TBXAS1 (p = 0.008) [1].
• Mutation of the NF-E2 site greatly reduced TXAS promoter activity in these two types of cells [22].
• This has led to speculation regarding possible linkage of COX isozymes with PGE and TXA synthase [21].

Analytical, diagnostic and therapeutic context of TBXAS1

• Levels of TBXA2R and TBXAS1 transcripts were quantified using quantitative real-time RT-PCR analysis and correlated with clinical/pathological information including nodal status, grade, prognosis and long term survival (median follow-up period 120 months) [1].
• Binding of the peptide antibodies to recombinant TXS in transfected COS-1 and to endogenous TXS in THP-1 cells was analyzed by immunocytochemistry [20].
• The resulting peptide antibodies were highly specific and recognized human TXS, as shown by binding assays and Western blot analysis [20].
• Indirect end labeling and ligation-mediated PCR analyses further demonstrated that the occupation of TXAS promoter NF-E2 site was associated with disruption of nucleosomal structure [23].
• Molecular cloning of human platelet thromboxane A synthase [24].

References