[Show abstract][Hide abstract] ABSTRACT: Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies.
[Show abstract][Hide abstract] ABSTRACT: During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.
Journal of Korean medical science 09/2015; 30(9):1308-12. DOI:10.3346/jkms.2015.30.9.1308 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A three layer cathode is a promising stack structure for long lifetime and high efficiency in organic light-emitting diodes. The interfacial chemical reactions and their effects on electronic structures for alkaline-earth metal (Ca, Ba)/Alq3 [tris(8-hydroxyquinolinato)aluminum] and Ca/BaF2/Alq3 are investigated using in-situ
X-ray and ultraviolet photoelectron spectroscopy, as well as molecular model calculation. The BaF2 interlayer initially prevents direct contact between Alq3 and the reactive Ca metal, but it is dissociated into Ba and CaF2 by the addition of Ca. As the Ca thickness increases, the Ca penetrates the interlayer to directly participate in the reaction with the underlying Alq3. This series of chemical reactions takes place irrespective of the BaF2 buffer layer thickness as long as the Ca overlayer thickness is sufficient. The interface reaction between the alkaline-earth metal and Alq3 generates two energetically separated gap states in a sequential manner. This phenomenon is explained by step-by-step charge transfer from the alkaline-earth metal to the lowest unoccupied molecular orbital states of Alq3, forming new occupied states below the Fermi level.
[Show abstract][Hide abstract] ABSTRACT: Nephrin is the signature molecule in the podocyte of the glomerulus that forms the renal slit diaphragm, the main functional unit of the glomerulus. The present study focused on the expression of nephrin in the human placenta, which may also have a role in filtration and the maintenance of homeostasis in the kidneys. A total of nine placentas from normal healthy pregnant females at full term were investigated. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed. The expression of nephrin mRNA was relatively increased in the chorion compared with that in the villi and the amnion. The nephrin gene was detected in the villous cytotrophoblast cells and the endothelium of the intravillous vessels. It was also present in the chorionic and amniotic membranous lining, with its distribution being particularly dense in the amniocytes. The identification of nephrin in the human placenta, particularly at the maternal‑fetal interface, provides a novel insight into the molecular basis of the selective permeability of the placental barrier, which requires further elucidation.
Molecular Medicine Reports 07/2015; 12(4). DOI:10.3892/mmr.2015.4044 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether smoking is a risk factor for female sexual dysfunction (FSD) and to determine the relationship between the cumulative smoking dose and FSD in premenopausal women.
The study population consisted of sexually active premenopausal women. The frequency of FSD and female sexual function index (FSFI) total score were evaluated according to the smoking status (never/former and current smokers). Evaluation of sexual function was done using FSFI questionnaire, and women with FSFI score of ≤26.55 were considered to have FSD. In current smokers, sexual function was also evaluated according to the cumulative smoking dose and nicotine dependency.
A total of 900 women were included, and the frequency of current smokers and the frequency of FSD were 62 (6.9%) and 496 (55.1%), respectively. In current smokers, the frequency of FSD was significantly higher and the median total FSFI score was significantly lower than in never/former smokers, and this difference of FSD remained significant after adjustment for confounding variables. Among current smokers, the cumulative smoking dose (pack-years) and the total FSFI score showed negative correlation, in which increased cumulative smoking dose was associated with lower total FSFI score (r=-0.278, P<0.05). In terms of nicotine dependency, the total FSFI score of moderately to heavily nicotine dependent smokers was significantly lower than that of lightly dependent smokers.
In premenopausal women, current smoking was an independent risk factor for FSD. And cumulative smoking dose and nicotine dependency were associated with higher risk of FSD.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have suggested that subclinical hypothyroidism is associated with the risk of anxiety or depression and can affect quality of life. However, there is a paucity of information regarding the relationship between subclinical hypothyroidism and female sexual dysfunction.
The study population consisted of sexually active middle-aged women (≥40 years old) who visited the center for health promotion and optimal aging at Seoul National University Hospital for a health check-up between 2010 and 2011. Sexual function was evaluated by the female sexual function index (FSFI) questionnaire, and female sexual dysfunction was defined as a FSFI score of ≤26.55. FSFI scores and female sexual dysfunction frequencies were compared between cases with subclinical hypothyroidism and healthy controls. Nonparametric methods were used for statistical analysis.
A total of 1086 women were included, and the frequency of subclinical hypothyroidism and female sexual dysfunction was 138 (12.7%) and 741 (68.2%), respectively. The total FSFI score and the scores in each domain were not different between the two groups (median total FSFI score (interquartile range): 23.8 (20.2-27.5) for normal thyroid status vs. 24.4 (20.6-27.6) for subclinical hypothyroidism, p=n.s.). The frequency of female sexual dysfunction was not different between the two groups, either (68.4% for normal thyroid status vs. 67.4% for subclinical hypothyroidism, p=n.s.). These findings were consistent even after adjustment for confounding variables.
Subclinical hypothyroidism is not a risk factor for sexual dysfunction in middle-aged women.
Thyroid: official journal of the American Thyroid Association 06/2015; 25(7). DOI:10.1089/thy.2015.0015 · 4.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea.
Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system.
A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%).
Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.
[Show abstract][Hide abstract] ABSTRACT: Presenting twins are less likely to develop respiratory complications than non-presenting twins. The precise reason for this difference is not well understood, although it is known that the presence of inflammation reduces the risk of respiratory morbidity at birth. To further investigate this association, we compared the concentrations of inflammatory biomarkers in mid-trimester amniotic fluid (AF) of asymptomatic twin pairs.
The study population consisted of women with twin pregnancies who underwent mid-trimester amniocentesis (15-20 weeks) for routine clinical indications and delivered at term. AF was analyzed for pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IFN-γ, TNF-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12), and chemokines (Complement Factor D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, CRP, CCL2/MCP-1, Leptin, Resistin) using Luminex Performance Assay multiplex kits. Data were analyzed using Wilcoxon signed rank test.
A total of 82 twin pairs were enrolled. Mid-trimester AF concentrations of IL-8, MMP-8, CRP, MCP-1, leptin, and resistin were significantly higher in the presenting twin compared with the non-presenting twin (p<0.05 for each). Differences in AF concentrations of IL-8, MMP-8, and CRP persisted after adjustment for the fetal growth restriction at the time of birth and chorionicity.
These data suggest that, as early as the mid-trimester, the presenting fetus in an otherwise uncomplicated twin pregnancy is exposed to higher levels of pro-inflammatory mediators (especially IL-8, MMP-8, and CRP) than its non-presenting co-twin. Whether this pro-inflammatory milieu reduces the risk of neonatal respiratory morbidity at birth or has other functional implications needs to be further evaluated.
American Journal of Obstetrics and Gynecology 01/2015; 212(1):S271. DOI:10.1016/j.ajog.2014.10.589 · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report high-quality GaN crystal grown directly on graphene layers without a buffer layer by metal-organic chemical vapor deposition. Photoluminescence and Raman spectra reveal that GaN crystal grown on graphene layers has mild strain compared to that grown on sapphire and SiO2 substrate. Etch pit was not observed on the surface of GaN/graphene where the threading dislocations were diminished inside the bulk, which is markedly different from GaN/sapphire with threading dislocations present on GaN surface. This opens a new possibility that graphene with pi electron and hexagonal symmetry could be an ideal substrate for GaN crystal growth, instead of using expensive sapphire substrate.
[Show abstract][Hide abstract] ABSTRACT: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector.
Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon’s AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), β-human chorionic gonadotrophin (β-hCG), and prolactin] were measured.
(1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P
Journal of Perinatal Medicine 11/2014; 43(4). DOI:10.1515/jpm-2014-0276 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Drep2 is a novel nuclease from the fruit fly that might have a similar function in apoptosis to DFF40 and DFF45, which are primary players in apoptotic DNA fragmentation. Drep2 contains a conserved CIDE domain of ∼90 amino-acid residues that is involved in protein–protein interaction. In this study, the Drep2 CIDE domain was purified and crystallized by the hanging-drop vapour-diffusion method. X-ray diffraction data were then collected to a resolution of 2.3 Å. The crystals were found to belong to the orthorhombic space group P212121, with unit-cell parameters a = 50.28, b = 88.70, c = 113.37 Å.
[Show abstract][Hide abstract] ABSTRACT: To develop an ultrasonographic severity scoring of non-immune hydrops in order to predict perinatal outcomes in women with non-immune hydrops.
The study population consisted of pregnant women who were admitted and delivered with the diagnosis of fetal non-immune hydrops and singleton gestation. Cases were divided into “perinatal survivor” and “perinatal non-survivor” groups. Perinatal non-survivor cases were defined as those with stillbirth or neonatal death ≤28 completed days after birth. The presence of an abnormal fluid collection in each body compartment, such as subcutaneous edema, pleural effusion, pericardial effusion, or ascites was assigned a score of 1 point per each body compartment, and the absence of abnormal fluid collection was scored as 0 point. The total number of abnormal fluid collections was converted to a numeric score, which was called the ultrasonographic severity scoring of non-immune hydrops (USNIH).
Perinatal death occurred in 46.5% (20/43) of the cases of non-immune hydrops. USNIH in patients of the non-survivor group was significantly higher than that in those of the survivor group [non-survivor group 3 (2–4) vs. survivor 2 (2–3); median (range); P
Journal of Perinatal Medicine 05/2014; 43(1). DOI:10.1515/jpm-2013-0208 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence of uric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction. Uric acid inhibited insulin-induced endothelial nitric oxide synthase (eNOS) phosphorylation and NO production more substantially than endothelin-1 expression in HUVECs, with IC50 of 51.0, 73.6, and 184.2, respectively. Suppression of eNOS phosphorylation and NO production by uric acid was PI3K/Akt-dependent, as verified by the transfection with p110. Treatment of rats with the uricase inhibitor allantoxanamide induced mild hyperuricemia and increased mean arterial pressure by 25%. While hyperuricemic rats did not show systemic insulin resistance, they showed impaired vasorelaxation induced by insulin by 56%. A compromised insulin response in terms of the Akt/eNOS pathway was observed in the aortic ring of hyperuricemic rats. Coadministration with allopurinol reduced serum uric acid levels and blood pressure and restored the effect of insulin on Akt-eNOS pathway and vasorelaxation. Taken together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin-induced NO production, potentially leading to the development of hypertension.-Choi, Y.-J., Yoon, Y., Lee, K.-Y., Hien, T. T., Kang, K. W., Kim, K.-C., Lee, J., Lee, M.-Y., Lee, S. M., Kang, D.-H., Lee, B.-H. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.
The FASEB Journal 03/2014; 28(7). DOI:10.1096/fj.13-247148 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the success rate of the "intended conservative management strategy" of ruptured ovarian cysts with hemoperitoneum and the risk factors for surgical interventions in healthy women of reproductive age.
Patients who visited the emergency department with abdominal pain and were diagnosed with a ruptured ovarian cyst with hemoperitoneum between August 2008 and June 2013 were included in this retrospective study. The diagnosis of the ruptured ovarian cysts and hemoperitoneum was based on the clinical symptoms, physical examination and ultrasound and CT imaging. The rate of surgical interventions and the risk factors for surgical intervention were determined.
A total of 78 women were diagnosed with a ruptured ovarian cyst with hemoperitoneum. Most patients (80.8%, 63/78) were managed conservatively, and 19.2% of the patients (15/78) required a surgical intervention. In the multiple logistic regression analysis, the diastolic blood pressure (dBP) (odds ratio [OR] of 0.921 with 95% confidence interval [CI] of 0.855-0.993) and the depth of the total pelvic fluid collection in CT (DTFC_CT) (OR 1.599 with 95% CI 1.092-2.343) were the significant determining factors of surgical intervention after adjustment. The rate of surgical intervention was 6.5% vs. 15.8% vs. 77.8% in the patients with neither dBP≤70 mmHg nor DTFC_CT≥5.6 cm, those with only one of those features, and those with both, respectively.
Most cases of ruptured ovarian cysts with hemoperitoneum can be managed conservatively. A low diastolic blood pressure and a large amount of hemoperitoneum suggest the need for surgical intervention.
PLoS ONE 03/2014; 9(3):e91171. DOI:10.1371/journal.pone.0091171 · 3.23 Impact Factor