• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.110-115
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• 2008

Purpose: Intussusceptions are one of the most common causes of intestinal obstruction in infants and young children. Although it is easily treated by non-operative reduction using barium, water or air, this treatment is very stressful for young patients and may cause bowel perforation, peritonitis and shock. In this study, we identified the risk factors associated with the failure of non-operative reduction, to identify a group of children that would benefit from the procedure and those who would not. Methods: We reviewed the medical records of patients with intussusception who were treated at the Korea University Medical Center Ansan hospital from March 1998 to July 2006. Three hundred fourteen children with intussusception were identified. Among them, non-operative reductions were performed in three hundred. Clinical and radiological variables were compared according to the failure or success of the non-operative reduction. Results: Non-operative reductions were successful in 243 (81%) and failed in 57 (19%). The group that had failed procedures had a younger age (12.3${\pm}$17.2 months vs. 18.0${\pm}$15.8 months, p=0.03), longer symptom duration before reduction (33.6${\pm}$29.0 hr vs. 21.5${\pm}$20.3 hr, p<0.01), more vomiting and lethargy (p<0.01), but less abdominal pain and irritability (p<0.01), compared with the group that had a successful procedure. Logistic regression analysis showed that the factors associated with the failure of non-operative reductions were a younger age, less than 6 months of age (odds ratio: 2.5, 95% confidence interval: 1.2~5.2, p=0.01), duration of symptoms, longer than 24 hrs before reduction (odds ratio: 2.1, 95% confidence interval: 1.2~4.2, p=0.03), bloody stool (odds ratio: 4.8, 95% confidence interval: 1.9~12.2, p<0.01), lethargy (odds ratio: 3.4, 95% confidence interval: 1.1~10.4, p=0.04), and abdominal pain or irritability (odds ratio: 0.2, 95% confidence interval: 0.1~0.4, p<0.01). Conclusion: For children with intussusception, an age younger than 6 months, and duration of symptoms more than 24 hrs before reduction, as well as the presence of bloody stools, lethargy and abdominal pain or irritability were variables associated with failure of a non-operative reduction. Knowledge of these variables should be considered in making clinical decisions for therapeutic interventions.