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Tuesday, 17 December 2013

The Effects of Hormone Thromboxane (1)

Thromboxane
Thromboxane is memeber of  member of the family of lipids known as eicosanoids, containing 2 major thromboxanes, Thromboxane A2, a potent stimulator of platelet aggregation, and thromboxane B2,  a metabolite of thromboxane A2 which is known to be highly unstable under physiological conditions.
1. The thromboxane synthase and receptor signaling pathway in cancer
Thromboxane A(2) (TXA(2)) is a biologically active metabolite of arachidonic acid formed by the action of the terminal synthase, thromboxane A(2) synthase (TXA(2)S), on prostaglandin endoperoxide (PGH(2)). TXA(2) is responsible for multiple biological processes through its cell surface receptor, the T-prostanoid (TP) receptor. According to the study by the Wayne State University, potential involvement of TXA(2)S and TP in tumor progression, especially tumor cell proliferation, migration, and invasion that are key steps in cancer progression. In addition, the regulation of neovascularization by TP has been identified as a potent source of control during oncogenesis(1).

2. Pesveratrol to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes
Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. In the study to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity and the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol, found that resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol(2).

3. Thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform and Bladder cancer
Increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform are found in the tissues of patients with bladder cancer. In the study by the University of South Carolina to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients, found that increased levels of thromboxane B(2) (TXB(2)) the major metabolite of TXAS and increased levels of the TPβ receptor. These results raised the possibility that patients with bladder cancer may be followed for progression or remission of their disease by quantitation of these substances in their urine(3).

4. Thromboxane synthase  and Non small cell cancer
Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. In the study toexamine the TXS expression in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression, indicated that TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC(4).

5. Endogenous levels of AA and selected eicosanoids and colon cancer
Cumulative evidence shows that eicosanoids such as prostaglandins, leukotrienes, thromboxanes and hydroxy eicosatetraenoic acids play an important role in associating inflammation with human colorectal cancer (CRC). In the study In the study of an ultra-pressure liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the targeted profiling of eight relevant eicosanoids and the major metabolic precursor, arachidonic acid (AA), in human colon, applied for the clinical profiling of matched pairs of cancerous and normal colon mucosae obtained from eight colorectal cancer patients, indicated that Endogenous levels of AA and selected eicosanoids such as prostaglandin E(2) (PGE(2)), prostacyclin (PGI(2)) [assayed as its stable hydrolytic product 6-keto-prostaglandin(1α) (6-k PGF(1α))] and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) were found to be significantly different (p <0.05; paired t-test) between cancerous and normal mucosae(5).

6. The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer
The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer is poorly understood. In the study to examine the role of TxA(2) in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells, found that  NNK stimulates TxA(2) synthesis and activates its receptor in lung cancer cells. The increased TxA(2) may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells(6).

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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22037941
(2) http://www.ncbi.nlm.nih.gov/pubmed/23617069
(3) http://www.ncbi.nlm.nih.gov/pubmed/21983220
(4) http://www.ncbi.nlm.nih.gov/pubmed/21388528
(5) http://www.ncbi.nlm.nih.gov/pubmed/21337637
(6) http://www.ncbi.nlm.nih.gov/pubmed/20818420