Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model.
Sphincter of Oddi manometry (SOM) is the gold standard for assessing sphincter of Oddi dysfunction (SOD), but is considered a diagnostic sensitivity of 30-80% and associated with significant complications of pancreatitis. Electromyography (EMG) of sphincter of Oddi (SO) using a circular electrode (CE) may be useful in improving diagnostic accuracy and reducing complications. To evaluate the feasibility and reliability of the CE, we record myoelectric activity of SO in rabbits using the CE to compare with the traditional needle electrode (NE). The CE was prepared using a double-channel biogel catheter with two silver rings at the head of the catheter. The CE was then inserted into the lumen of the SO through the duodenal papilla, and myoelectric activity was recorded in the SO in 30 rabbits. An EMG recorded using an NE was performed at the same time, when the SO was in basal state, after injection of cholecystokinin and N-butylscopolamine bromide. Electromyographs recorded by the two methods were then evaluated. Satisfactory SO EMGs were acquired using the CE without any injury. Simultaneous recording revealed a very similar traces and one-to-one correspondence of SO spike bursts (SOSB). Linear regression analysis showed a significant direct correlation between the two methods for SOSB duration and amplitude. The results suggested that CE was comparable with NE in terms of recording efficacy. The CE also has advantages of easy fixation, accurate localisation, broad applicability and ease of achieving satisfactory outcomes without trauma, compared with the NE.
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