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Left atrial appendages are formations greatly varying in volume and shape. This variability should be considered when interpreting images of the left atrial appendage, and in particular when diagnosing thrombi.

S U M M A R Y 1,25-dihydroxyvitamin D 3 has anti-mitotic, pro-differentiating, and proapoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D 3 -synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high-to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D 3 could prevent intestinal tumor formation and progression. An adequate 1,25-D 3 serum level is essential to maintain calcium homeostasis. Because of the hormone's anti-mitotic, pro-differentiating, pro-apoptotic activity, it has also been suggested to provide protection against tumor progression (Lamprecht and Lipkin 2003). However, treatment of tumor patients with 1,25-D 3 or with synthetic vitamin D analogues is not feasible due to the hypercalcemic effect at the pharmacological (nanomolar) doses necessary to achieve antimitotic action. Recently, another physiological link between vitamin D and cancer prevention and/or therapy has been found. In addition to the kidney, several other tissues express enzymes necessary for vitamin D synthesis. We were the first to demonstrate that human colonocytes in culture are able to synthesize 1,25-D 3 from 25-D 3 (Cross et al. 1997) and that in freshly isolated colon tumor cells a wide spectrum of vitamin D metabolites is present ). Our further studies by semiquantitative RT-PCR showed increasing levels of CYP27B1 and of VDR mRNA during early colon tumor progression . CYP27B1 mRNA was overexpressed also in cervical, breast, and ovarian carcinomas compared with normal tissue (Friedrich et al. 2003). This suggested to us an autocrine/paracrine protective effect of 1,25-D 3 synthesized in colon tumor cells during premalignancy and early malignancy. In late-stage high-grade colon cancer there is apparent failure of this protective system ). However, with present methodology it is not possible to verify this by measuring tissue accumulation of 1,25-D 3 .In view of our preliminary observations and the fact that the expression level of CYP27B1 seems to be related to the level of cell differentiation, at least in human colon tumor cell cultures (Bareis et al.

Expression of dihydropyrimidine dehydrogenase (DPD) displays a regular daily oscillation in nonmalignant cells. In colorectal cancer cells, the expression of this 5-fluorouracilmetabolizing enzyme is decreased, but the reason remains unclear. In this study, we analyzed by real-time reverse transcription-PCR (RT-PCR) the expression of DPD and of members of the cellular oscillation machinery, period 1 (Per1), period 2 (Per2), and CLOCK, in primary colorectal tumors and normal colon mucosa derived from the same patients. Analysis of tumors according to differentiation grade revealed a 0.46-fold (P = 0.005) decrease for DPD mRNA and a 0.49-fold (P = 0.004) decrease for Per1 mRNA in undifferentiated (G3) tumors compared with paired normal mucosa. In this tumor cohort, the correlation between DPD and Per1 levels was r = 0.64, P < 0.01. In moderately differentiated (G2) colon carcinomas, reduction of DPD and Per1 mRNA levels did not reach significance, but a significant correlation between the respective mRNA levels was detectable (r = 0.54; P < 0.05). The decrease and correlation of DPD and Per1 mRNA levels were even more pronounced in female (G3) patients (DPD: female, 0.35-fold, P < 0.001 versus male, 0.58-fold, P < 0.05; and Per1: female, 0.47-fold, P < 0.01 versus male, 0.52-fold, P < 0.01). The highly significant correlation of DPD mRNA with Per1 mRNA expression suggests control of DPD transcription by the endogenous cellular clock, which is more pronounced in women. Our results also revealed a disturbed transcription of Per1 during tumor progression, which might be the cause for disrupted daily oscillation of DPD in undifferentiated colon carcinoma cells. [Cancer Res 2007;67(16):7917-22]

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