Pharmacological characterization of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmeth oxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM103), a novel selective 5-lipoxygenase-activating protein inhibitor that reduces acute and chronic inflammation.
(66/135)
The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia.
(68/135)
Cancer stem cells (CSCs) are believed to be the initiating cells for many types of blood cancer and some solid tumors, and curative therapies of these cancers require eradicating CSCs. Specific targeting of CSCs but not normal stem cell counterparts is a correct strategy for developing new anti-cancer therapies, and the success of this approach relies on identification of specific target genes in CSCs. Using BCR-ABL-induced chronic myeloid leukemia (CML) as a cancer model, we recently identified arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSCs) in CML. Without Alox5, BCR-ABL fails to induce CML in mice due to the impairments of the functions of LSCs. The lack of Alox5 does not significantly affect the functions of normal hematopoietic stem cells. In addition, Zileuton, a specific 5-LO inhibitor, also causes the impairments of the functions of LSCs in a similar manner. Our results prove the principle that CSC-specific genes that play key roles in cancer development can be identified and inhibition of these genes can lead to eradication of these cells for cure. Here, we further discuss the mechanisms of Alox5 in CML, and the use of Zileuton as a potential and promising drug in eradicating LSCs in CML and other myeloproliferative diseases. We believe that our discovery of the role of Alox5 in regulating the function of LSCs in CML reminds us of viewing CSCs at a different angel. We predict that CSCs in other types of cancer also utilize specific regulatory pathways to control their survival and self-renewal, and inhibition of these pathways profoundly suppresses CSCs but not their normal stem cell counterparts. Specific targeting of CSCs without causing significant harm to normal stem cells should be a correct direction to go in developing novel therapeutic strategies in the future. (+info)
The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells.
(69/135)
5-Lipoxygenase pathway gene polymorphisms: lack of association with asthma in a Spanish population.
(71/135)
BACKGROUND: Cysteinyl-leukotrienes are mediators of inflammatory responses in bronchial asthma. We studied the genes encoding the enzymes involved in their synthesis to identify risk factors for asthma. The promoter polymorphisms LTC4S -444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 have been reported to be associated with bronchial asthma. METHODS: We analyzed the effects of LTC4S -444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 on asthma susceptibility by means of a case-control study with 193 ethnically matched, unrelated individuals. Participants were classified as severe asthmatics, nonsevere asthmatics, and nonasthmatics, using a combination of 2 techniques: polymerase chain reaction-restricted fragment length polymorphism and multiplex capillary electrophoresis. RESULTS: No association was found between these polymorphisms and asthma, neither individually nor in combination. CONCLUSION: Although the studied polymorphisms have been previously reported to constitute risk factors for the disease, we found no association between LTC4S -444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 polymorphisms and bronchial asthma. (+info)
Regulation of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase-activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic chondrocytes.
(72/135)