BackgroundCancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors.MethodsOvarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test.ResultsEach cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens.ConclusionsOvarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.

The binding of calcium-calmodulin (CaCaM) to various cation channels has been found to modulate the channel function. Recently, the anion permeability of the TMEM16A calcium-activated chloride channel was also reported to be altered upon modulation by CaCaM (Jung et al., Proc Natl Aca Sci: 110: 360-365, 2013). This modulation effect could be physiologically important for many cellular functions that involve the TMEM16A channel. To study the modulation of TMEM16A by CaCaM, we expressed the TMEM16A channel in HEK 293 cells and performed excised inside-out patch recordings. The anion permeability ratios were evaluated based on the reversal potentials in bi-ionic conditions in which various anions were placed in the intracellular side with an equal concentration of chloride ions in the extracellular solution. We used both the voltage-clamp and the currentclamp (I=0) recording approaches, and surprisingly found that CaCaM, when applied to the intracellular side of the channel, did not alter reversal potentials. The activity of CaCaM was verified by a positive control experiment in which the current of the olfactory cyclic nucleotide-gated channel encoded by CNGA2 was inhibited upon the application of intracellular CaCaM. These results contradict the recent finding that intracellular CaCaM alters the anion permeability of the TMEM16A channel. Our experiments also show that the measurement of reversal potentials is imprecise if the recorded current is > 1-2 nA at þ40 mV, likely due to a series-resistance problem. We notice that the reversal potential change in Jung et al is particularly prominent at high intracellular [Ca 2þ ], which activates huge calcium-activated currents (>5-10 nA) in whole-cell configurations. Whether this technical issue causes the change of the reversal potential in Jung et al. requires further scrutiny. 733-Pos Board B488Serine 550 is Involved in the Regulation of Mouse TMEM16A-Caccs by CaMKII

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