Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Objective: : Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. Methods: : This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4–6 despite of successful reperfusion). Results: : In a total of 214 participants, older age (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.56 to 3.67; p<0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR, 1.12; 95% CI, 1.04 to 1.21; p=0.004), very poor collateral perfusion grade (OR, 35.09; 95% CI, 3.50 to 351.33; p=0.002), longer door-to-puncture time (OR, 1.08; 95% CI, 1.02 to 1.14; p=0.009), and failed reperfusion (OR, 3.73; 95% CI, 1.30 to 10.76; p=0.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI, 1.44 to 3.67; p<0.001), higher baseline NIHSS scores (OR, 1.12; 95% CI, 1.03 to 1.22; p=0.006), very poor collateral perfusion grade (OR, 4.96; 95% CI, 1.42 to 17.37; p=0.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI, 1.03 to 1.15; p=0.003) were associated with unfavorable functional outcomes. Conclusion : The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

No abstract available.
Cardiomyopathies ; Child ; Female ; Heart-Assist Devices ; Humans ; Leukemia

PURPOSE: Although microalbuminuria is known as a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated the incidence and reference range of microalbuminuria in healthy children. This study aimed to establish a reference range and to study the age-related trend for spot urine microalbumin/creatinine ratio in a Korean pediatric population. MATERIALS AND METHODS: 352 healthy children were studied from July 2007 through March 2010. Height, weight, serum creatinine, spot urine microalbumin/creatinine ratio, and glomerular filtration rate (GFR) were obtained for each subject. We divided the study population into 5 groups according to age, and compared the spot urine microalbumin/creatinine ratio with other variables using one-way analysis of variance (ANOVA), regression analysis and Pearson's correlation analysis. RESULTS: In this study, the data showed that the spot urine microalbumin/creatinine ratio decreased with age: 1-12 months, 22.72+/-13.80 mg/mmol (2SD: 3.33-54.40 mg/mmol); 13-28 months, 16.34+/-9.58 mg/mmol (2SD: 3.16-35.19 mg/mmol); 29-48 months, 13.12+/-9.74 mg/mmol (2SD: 3.01-41.57 mg/mmol); 4-6 years, 10.58+/-8.13 mg/mmol (2SD: 0.00-30.19 mg/mmol); and 7-19 years, 5.13+/-5.44 mg/mmol (2SD: 0.45-14.45 mg/mmol). The spot urine microalbumin/creatinine ratio showed correlation with age, height, height z-score, weight, weight z-score, GFR, body mass index (BMI) and body surface area (BSA). CONCLUSION: The spot urine microalbumin/creatinine ratio in normal Korean children decreased with age. This ratio could potentially be used to establish reference ranges and cutoff values for Korean children and to predict nephropathy and cardiomyopathy.
Adolescent ; Age Factors ; Albuminuria/*epidemiology ; Analysis of Variance ; Child ; Child, Preschool ; Creatine/urine ; Female ; Glomerular Filtration Rate ; Humans ; Infant ; Male ; Reference Values ; Regression Analysis ; Republic of Korea/epidemiology ; Young Adult

BACKGROUND/AIMS: To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. METHODS: Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer ifferences in individual susceptibility to smoking were estimated using a susceptibility index formula. RESULTS: Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV1, liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 +/- 19.2 vs. 42.9 +/- 21.7 for pack-years; 1.4 +/- 0.5 vs. 2.0 +/- 0.6 for FEV1; 3.0 +/- 0.7 vs. 2.0 +/- 0.6 for FVC; 4.5 +/- 0.8 vs. 5.7 +/- 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 +/- 4.1 vs. 0.7 +/- 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). CONCLUSIONS: The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.
Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Cohort Studies ; Female ; *Gender Identity ; Humans ; Korea/epidemiology ; Lung Neoplasms/complications/*epidemiology/pathology ; Lung Volume Measurements ; Male ; Middle Aged ; Respiratory Function Tests ; Risk Assessment ; Sex Factors ; Smoking/*adverse effects/epidemiology

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 < or = 250), bilateral lung infiltration, and old age (> or = 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of > or = 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of > or = 13. As a prediction rule, the presence of > or = 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.
APACHE ; Adult ; Aged ; Antiviral Agents/therapeutic use ; Female ; Hospitalization ; Humans ; Influenza A Virus, H1N1 Subtype/*isolation & purification ; Influenza, Human/drug therapy/*epidemiology/mortality ; Intensive Care Units ; Male ; Middle Aged ; Pandemics ; Predictive Value of Tests ; ROC Curve ; Respiration, Artificial ; Risk Factors ; Severity of Illness Index

In this study, the effects of a mixture consisting of vitamin E, vitamin C, pycnogenol and evening primrose oil (mixture LGNC-5) on ultraviolet light (UV) induced pigmentation and wrinkle reductions of normal healthy volunteers were studied. In a double-blind placebo-controlled study, each of 54 subjects took daily either 4 capsules of the mixture LGNC-5 (Group ABC; 282.5 mg/capsule) or placebo (Group Ganada). We irradiated 2.5 MED UV on the upper arms and measured the whitening effect by colorimeter-based L value. The level of wrinkle reduction was determined by image analysis using skin replica around the crow' feet, and the level of serum vitamin E was determined at baseline and 12 weeks. After 12-week oral administration, the treated group showed a significant reduction in skin pigmentation and wrinkles compared with the placebo group (p = 0.011 and p = 0.000005 , respectively). Also, the level of serum vitamin E was significantly increased in the treated group after 12-week oral adminstration of the mixture compared with that in the placebo group (p = 0.0001). In conclusion, 12-week oral administration of LGNC-5 as a dietary supplement could be effective to reduce both UV induced pigmentation and skin wrinkle without side effects.
Administration, Oral ; Arm ; Ascorbic Acid ; Capsules ; Dietary Supplements ; Flavonoids ; Foot ; gamma-Linolenic Acid ; Humans ; Linoleic Acids ; Oenothera biennis ; Pigmentation ; Plant Oils ; Skin ; Skin Pigmentation ; Ultraviolet Rays ; Vitamin E ; Vitamins

PURPOSE: This study evaluated the benefit of radiation therapy in high-risk breast cancer patients who have received immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. The evaluation involved examining the effect of radiation therapy on postmastectomy flap fat necrosis and tumor recurrence. METHODS: A retrospective review was performed on 102 patients who underwent mastectomy and immediate TRAM flap reconstruction between 1996 and 2001 at the Asan Medical Center (Seoul, Korea). The mean patient age was 41 years, and the median follow-up time was 33 months. Skin-sparing mastectomy was con ducted in 82 patients (80.4%) and classical mastectomy in 20 patients (19.6%). Of the 21 high-risk patients needing postmastectomy radiation therapy, nine received it. RESULTS: Moderate or severe TRAM flap fat necrosis occurred more frequently in patients receiving radiation therapy than those not receiving radiation therapy (55.6% vs. 19.4%, P=0.026). In the group with high-risk patients, two tumor recurrences occurred (one-locoregional and one-systemic). Among the 102 patients, thirteen had recurrences, including only two high-risk patients, with almost of them being systemic recurrences except four locoregional recurrences. CONCLUSION: Our findings showed that radiation therapy increased flap fat necrosis in high-risk patients underwent immediate TRAM flap reconstruction. Such necrosis can result in poor outcomes for reconstruction. We recommend careful consideration prior to using radiation therapy on high-risk breast cancer patients after immediate TRAM flap reconstruction, where clinicians need to balance the possible positive effects on recurrence with the possible negative effects on flap tissue.
Breast Neoplasms* ; Breast* ; Chungcheongnam-do ; Fat Necrosis* ; Follow-Up Studies ; Humans ; Mastectomy* ; Necrosis ; Rectus Abdominis ; Recurrence ; Retrospective Studies

BACKGROUND: Production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathology of autoimmune disease. It is unknown whether iNOS expression is increased within testes and whether iNOS and NO have essential roles in the pathogenesis of EAO. METHODS: EAO was induced in guinea pig testes at 17 days after secondary immunization by administration of crude extract (CE) and purified glycoprotein 1 (GP1) from normal guinea pig testes. iNOS gene expression was assessed by RT-PCR and Northern blot analysis in testes. Localization of iNOS and Mac-1 and the indicator of NO-mediated tissue injury, nitrotyrosine, were detected in the testicular lesion by immunohistochemistry. RESULTS: In control testes, inflammation and iNOS gene expression were not detected, whereas, in CE- and GP1-injected testes, inflammation and marked iNOS gene expression were evident at day 17 after secondary immunization. Immunohistochemistry of Mac-1 showed the colocalization with iNOS protein and nitrotyrosyl proteins in intertubules, suggesting that NO produced by infiltrated macrophages may be involved in inflammatory lesions of intertubules. Intraperitoneal administration of aminoguanidine significantly prevented EAO with reduction of inflammation, iNOS expression and nitrotyrosine formation. CONCLUSION: These results suggest that NO production by macrophages may be important in the pathogenesis of CE- and GP1-induced EAO. Furthermore, this study demonstrated the therapeutic potential of iNOS inhibitor in the treatment of inflammatory and autoimmune mediated-diseases.
Animals ; Autoimmune Diseases ; Blotting, Northern ; Gene Expression ; Glycoproteins ; Guinea Pigs* ; Guinea* ; Immunization, Secondary ; Immunohistochemistry ; Inflammation ; Macrophages ; Male ; Nitric Oxide Synthase ; Nitric Oxide* ; Orchitis* ; Pathology ; Peroxynitrous Acid ; Testis