The antiphase expression of cry1 and Bmal1 may be preserved in ovarian cancers. The combination of cry1 and Bmal1 expression might become a possible prognostic marker in epithelial ovarian cancer.

Abstract. Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline. PA acts as a second messenger in cell proliferation; therefore PLD is believed to play an important role in carcinogenesis. PLD activity has been reported to be elevated in human breast, gastric, renal cell and colorectal carcinomas, compared with adjacent non-neoplastic tissues. The activity of PLD was also correlated with nuclear grade in breast cancer, tumor size in gastric carcinoma, and nodal involvement and deeper invasion in colorectal carcinoma. However, the number of cases in each study was small. The aim of this study was to investigate the expression level of PLD2 and its association with clinicopathological features in human colorectal carcinoma. Ninety-seven colorectal carcinomas were obtained from surgery. Expression level of PLD2 was assessed by real-time PCR. The prognostic relevance of PLD2 expression level in patients with colorectal carcinoma was also analyzed by the survival analysis of mortality follow-up data covering the period 2000-2004. PLD expression level was varied from tumor to tumor. Expression level of PLD was significantly correlated with tumor size (P<0.05); it was independent of lymph node metastasis, extent of invasion, pathological classification, distant metastasis and Dukes' stage. PLD expression level was also significantly correlated with survival of patients with colorectal carcinoma (P<0.05). These findings suggested that PLD2 plays an important role in progression of colorectal carcinoma and that PLD2 could be a target for therapy in colorectal carcinoma.

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Angiogenesis is essential for tumor growth and metastasis, therefore, inhibition of angiogenesis has emerged as a new therapy to treat cancers. Although vascular endothelial cell growth factor (VEGF) induces tumor growth and metastasis by its angiogenic property, the mechanism(s) of circadian rhythm in angiogenesis has not been fully analyzed. Here we revealed that VEGF mRNA expression level, protein expression level and its promoter activity belonged to circadian rhythm in human colon carcinoma cell line, HCT116 cells. HIF (hypoxia inducible factor)-1 also underwent circadian oscillation at levels of mRNA and promoter activity. Co-transfection of Bmal1 and Clock enhanced HIF-1 luciferase activity, but not VEGF luciferase activity, indicating that VEGF is not a direct target of Bmal1/Clock. However, inhibition of HIF-1 by chrysin resulted in disappearance of VEGF circadian oscillation, suggesting that HIF-1 is involved in the regulation of the VEGF expression. Moreover, circadian oscillation of VEGF and HIF-1 was induced by 100 nM of dexamethasone. These results suggest the link between the circadian oscillation between VEGF and HIF-1 , raising a possible strategy for chronotherapy in clinic.

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