These data demonstrate the feasibility and potential utility of mutation/deletion/amplification screening in cfDNA using NGS and dPCR for the detection of tumor biomarkers in children with solid tumors. These markers also have the potential utility to evaluate complete resection after surgery.

Several lines of evidence have indicated that the prevalence of depression in diabetic subjects is higher than that in the general population, however, little information is available on the effects of antidepressants in diabetes. In the present study, the antidepressantlike effect mediated by the activation of 5-HT 1A receptors was examined using the tail suspension test in streptozotocin-induced diabetic mice. Long-lasting increases in 5-HT turnover rates were observed in the diabetic mouse midbrain and frontal cortex, but not in the hippocampus. Duration of immobility was significantly longer in diabetic than in nondiabetic mice in the tail suspension test. The 5-HT 1A receptor agonist ( 7 )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (3-30 mg/kg, i.p.) reduced the duration of immobility in nondiabetic mice, and this effect was completely antagonized by pretreatment with, a selective 5-HT 1A receptor antagonist. In contrast, 8-OH-DPAT (3 mg/kg-3 mg/kg, i.p.) was ineffective in diabetic mice. The selective 5-HT reuptake inhibitor fluoxetine (3-56 mg/kg, i.p.) reduced the duration of immobility in both nondiabetic and diabetic mice. However, fluoxetine was less effective in diabetic mice than in nondiabetic mice. WAY-100635 (30 mg/kg, s.c.) reversed the suppression of the duration of immobility by fluoxetine (30 mg/kg, i.p.) in nondiabetic mice. On the other hand, the anti-immobility effect of fluoxetine (56 mg/kg, i.p.) was not antagonized by WAY-100635 (30 mg/kg, s.c.) in diabetic mice. The selective 5-HT 2 receptor antagonist 6-methyl-1-(1-methylethyl)-ergoline-8b-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY53,857) (30 mg/kg, s.c.) reversed the anti-immobility effect of fluoxetine in both nondiabetic and diabetic mice. Spontaneous locomotor activity in diabetic mice was not different from that in nondiabetic mice. 8-OH-DPAT (30 mg/kg, i.p.), but not fluoxetine, increased the spontaneous locomotor activity in both nondiabetic and diabetic mice. The number of 5-HT 1A receptors in the mouse frontal cortex was unaffected by diabetes. Plasma corticosterone levels in diabetic mice were significantly higher than that in nondiabetic mice. These results suggest that the antidepressant-like effect mediated by 5-HT 1A receptors may be attenuated by diabetes.

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Abstract. Freezing behavior is thought to be a sign of fear in animals. We examined whether the freezing behavior during the elevated open-platform stress, which is a psychological stressor without painful stimulus, is modulated by serotonergic neurotransmission and would be a useful marker for screening anxiolytic and / or antidepressant. Male ICR mice (6 -8-week-old) were individually placed on an elevated open-platform and the duration of freezing behavior of mouse was measured for 10 min. Fluoxetine and citalopram, selective serotonin (5-HT) reuptake inhibitors, markedly decreased the duration of freezing. Fenfluramine, a 5-HT releaser, and 8-OH-DPAT, a potent 5-HT 1A -receptor agonist, also significantly decreased the duration of freezing. In contrast, the 5-HT-synthesis inhibitor p-chlorophenylalanine significantly increased the duration of freezing. Diazepam, a benzodiazepine anxiolytic, had no effect on the duration of freezing at doses having no effect on locomotor activity. Imipramine and clomipramine, tricyclic antidepressants, also did not affect the duration of freezing. Reboxetine, a selective noradrenaline reuptake inhibitor, significantly increased the duration of freezing. These results indicate that the activation of serotonergic neurotransmission attenuates the fear-related behavior in the elevated open-platform test, while the activation of noradrenergic neurotransmission increases the fearrelated behavior. In addition, this test is convenient for assaying anxiolytic drugs that affect serotonergic neurotransmission.