Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model.

Purpose: Arachidonic acid metabolism via the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways modulates cell growth and apoptosis. Many studies have examined the effects of COX inhibitors on human colorectal cancer, but the role of 5-LOX in colonic cancer development has not been well studied. The purpose of this study was to evaluate the expression of 5-LOX in colonic polyps and cancer and the effect of 5-LOX inhibition on colon cancer cell proliferation.

Effect of LY293111 in combination with gemcitabine in colonic cancer.

New adjuvant therapies are needed for the treatment of stage III colon cancer. The essential fatty acids, linoleic and arachidonic acid enhance tumorigenesis through the cyclooxygenase and lipoxygenase pathways. Leukotriene B4 (LTB4) is a product of 5-lipoxygenase (5-LOX) which has tumor-promoting effects.

Differential effects of calpain inhibitors on hypertrophy of cardiomyocytes.

Two inhibitors of the calcium-dependent cysteine protease, calpain, have markedly different effects on the extent of hypertrophy induced by the alpha-adrenergic agonist, phenylephrine, of cultured neonatal rat ventricular myocytes. E64c, an inhibitor of calpain and other cysteine proteases, stimulated the hypertrophy by 59%. PD 150606, a specific calpain inhibitor, reduced the hypertrophy by 38%.

Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway.

Several studies have suggested that high dietary fat intake, particularly essential fatty acids, is associated with pancreatic cancer development and growth. Our previous studies have demonstrated that blockade of either the 5-lipoxygenase (LOX) or 12-LOX pathway of arachidonic acid metabolism inhibited pancreatic cancer cell proliferation and induced apoptosis. This study investigated the underlying mechanisms for LOX inhibitor-induced apoptosis and the potential of LOX inhibitors as antipancreatic cancer agents using the athymic mice xenograft model.

Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells.

Purpose: The effects of leukotriene (LT) B4 and its receptor antagonist LY293111 on proliferation and apoptosis of human pancreatic cancer cells were investigated, both in vitro and in vivo.

Experimental Design: Six human pancreatic cancer cell lines (MiaPaCa-2, HPAC, Capan-1, Capan-2, PANC-1, and AsPC-1) were used. Expression of LTB4 receptors, BLT1 and BLT2, was measured by reverse transcription-PCR.

Ethnic differences in titratable acid excretion and bone mineralization.

Purpose: To test our hypothesis that differences in urinary calcium excretion among blacks and whites may be secondary to ethnic variations in acid (H(+)) metabolism and to prove that increases in titratable acid excretion would be found among individuals predisposed to the development of stress fractures.

Methods: We administered 8 g NH(4)Cl acutely to 11 black and 18 white healthy volunteers and measured urinary sodium, calcium, and acid excretions. We measured the Na(+)/H(+) antiporter activity using acid-loaded platelets as surrogate markers for this exchanger expressed in renal epithelial cells.