TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation induced by TFAP2C also promoted cell motility and migration, leading to malignant development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1) signaling was involved in TFAP2C/TGFBR1-induced tumorigenesis. These results were confirmed by an in vivo xenograft model and patient tissue samples. This study shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and consequent activation of PAK1 signaling.
Carcinogenesis* ; Cell Cycle ; Cell Movement ; Cell Survival ; Heterografts ; Humans ; Lung Neoplasms ; Lung* ; Microarray Analysis ; Phosphotransferases ; Prognosis ; Up-Regulation*

Cardiac calcified amorphous tumors (CATs) can arise in all four chambers of the heart. Cardiac CATs can cause diverse symptoms according to their locations, and mass or embolic effects. Pulmonary emboli arising from cardiac CATs have been reported, but the true incidence is unknown due to their rarity. Herein we report a rare case with diffuse CATs in the right ventricle which caused a calcific pulmonary embolism and right-sided heart failure. Echocardiography, chest non-contrast computed tomography, and cardiac magnetic resonance imaging helped us diagnose the CATs. We recommend the usefulness of a multimodality imaging approach to characterize intracardiac masses and their complications accurately.
Animals ; Cats ; Echocardiography ; Heart ; Heart Failure ; Heart Neoplasms ; Heart Ventricles ; Incidence ; Magnetic Resonance Imaging ; Pulmonary Embolism ; Thorax

BACKGROUND: The autonomic nervous system plays a central role in the maintenance of hemodynamic stability. Cardiac autonomic dysfunction may result in serious complications, such as sudden cardiac death. Heart rate variability (HRV) is sigificantly reduced in patients undergoing chronic hemodialysis (HD). The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on the autonomic nervous system in chronic HD patients. METHODS: Forty chronic HD patients were prospectively studied. The participants were divided into conventional HD and OL-HDF groups. They received regular high-flux HD or OL-HDF for 4-hour sessions, three times a week. Time-and frequency-domain measures of the 24-hour HRV were analyzed during the interdialytic period prior to postdilution OL-HDF and every 6 months for 24 months. The 7-year survival was also evaluated. RESULTS: Among the 40 participants, 15 patients in the HD group and 11 patients in the OL-HDF group completed the study. There was no difference in the baseline characteristics. After 24 months of treatment, beta2-microglobulin concentration decreased (from 33.4 +/- 15.2 mg/dL to 28.4 +/- 6.2 mg/dL, P = 0.02) in the OL-HDF group, while there was no change in the HD group In the HRV analysis, the frequency-domain HRV parameters increased significantly compared with baseline in the OL-HDF group [natural logarithmic high frequency (lnHF), 3.15 +/- 3.36 ms2 vs. 4.42 +/- 3.81 ms2; ln low frequency (LF), 3.56 +/- 3.17 ms2 vs. 4.78 +/- 3.99 ms2; ln very low frequency (VLF), 4.90 +/- 4.62 ms2 vs. 6.38 +/- 5.54 ms2; LF/HF ratio, 1.4 +/- 0.4 vs. 2.5 +/- 0.1]. The survival rate was similar between the groups. CONCLUSION: This study shows that OL-HDF improved autonomic nervous system dysfunction in chronic HD patients.
Autonomic Nervous System ; Death, Sudden, Cardiac ; Heart Rate* ; Heart* ; Hemodiafiltration* ; Hemodynamics ; Humans ; Kidney Failure, Chronic* ; Prospective Studies ; Renal Dialysis ; Survival Rate

PURPOSE: This study was conducted to monitor the development of Korean premature infant at six-month age and to explore factors related to developmental status of the premature infants. METHODS: Participants were 58 premature infants whose corrected age was six-months old and their mothers. The developmental states of infants were followed-up with the Korean Prescreening Developmental Questionnaire (KPDQ-II). Clinical characteristics of the infants were identified from the medical records. Other characteristics including Edinburgh Postnatal Depression Scale, husband's support, social support, and mother-infant attachment were assessed using self-report questionnaires from the mothers. RESULTS: Forty three percent of the infants were in the group of questionable status of development on the KPDQ-II. There were significant differences between the premature infants with normal developmental status and those with questionable developmental status depending on gender (χ2=5.03, p=.034), gestational age (t=2.59, p=.012), hospital stay (t=-2.08, p=.042), revised Neurobiologic Risk Score (t=-3.05, p=.004) and mother-infant attachment score (t=2.12, p=.040). CONCLUSION: Mother-infant attachment, as well as physiological state of premature infants, is an important variable in early development. Therefore, early monitoring for the development has to be done for physiologically vulnerable premature groups. Also, providing proper nursing support to improve maternal attachment needs to be considered.
Depression, Postpartum ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Length of Stay ; Medical Records ; Mothers ; Nursing ; Prospective Studies*

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.
Apoptosis ; DNA Damage ; Fingers ; Glioblastoma ; Heterografts ; Humans ; Lung Neoplasms ; Macrophages ; NF-kappa B ; Ribosomal Proteins ; Ubiquitin ; Ubiquitination

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in C(max), and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in C(max) and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.
Animals ; Area Under Curve ; Bile Ducts* ; Bile* ; Body Weight ; Child ; Female ; Humans ; Inflammation ; Liver Neoplasms* ; Liver* ; Male ; Mammary Glands, Human ; Rats* ; Rats, Sprague-Dawley ; Toxicokinetics ; Xenobiotics

Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains ( Animals ; Ceramides ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Epidermis ; Fatty Acids, Nonesterified ; Humans ; Hyperglycemia ; Kidney ; Liver ; Mice ; Receptors, Cytoplasmic and Nuclear ; Skin ; Stearoyl-CoA Desaturase ; Subcutaneous Fat

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.
Adult ; Animals ; Breast Neoplasms ; Cognition Disorders ; Cyclophosphamide ; Cytokines ; Doxorubicin ; Drug Therapy ; Female ; Hindlimb Suspension ; Hippocampus ; Humans ; Macrophages ; Memory ; Mice* ; Mood Disorders ; Neurogenesis ; Neurons ; Spine ; Survivors