In Vitro Chemosensitivity Using the Histoculture Drug Response Assay in Human Epithelial Ovarian Cancer

The choice of chemotherapeutic drugs to treat patients with epithelial ovarian cancer has not depended on individual patient characteristics. We have investigated the correlation between in vitro chemosensitivity, as determined by the histoculture drug response assay (HDRA), and clinical responses in epithelial ovarian cancer. Fresh tissue samples were obtained from 79 patients with epithelial ovarian cancer. The sensitivity of these samples to 11 chemotherapeutic agents was tested using the HDRA method according to established methods, and we analyzed the results retrospectively. HDRA showed that they were more chemosensitive to carboplatin, topotecan and belotecan, with inhibition rates of 49.2%, 44.7%, and 39.7%, respectively, than to cisplatin, the traditional drug of choice in epithelial ovarian cancer. Among the 37 patients with FIGO stage Ⅲ/Ⅳ serous adenocarcinoma who were receiving carboplatin combined with paclitaxel, those with carboplatin-sensitive samples on HDRA had a significantly longer median disease-free interval than patients with carboplatin- resistant samples (23.2 vs. 13.8 months, p＜0.05), but median overall survival did not differ significantly (60.4 vs. 37.3 months, p＝0.621). In conclusion, this study indicates that HDRA could provide useful information for designing individual treatment strategies in patients with epithelial ovarian cancer

Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia

AbstractARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia

Transcription Factor Sp1 Is Involved in Expressional Regulation of Coxsackie and Adenovirus Receptor in Cancer Cells

Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (−503/−498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression

Tetramethyl-O-scutellarin isolated from peels of immature Shiranuhi fruit exhibits anti-inflammatory effects on LPSinduced RAW264.7 cells

Purpose: To investigate the anti-inflammatory activity of the ethanol extract of the immature fruit of a citrus, Shiranuhi, and to identify the active ingredient.Methods: The immature Shiranuhi peel was extracted with 80 % ethanol, and the extract was fractionated with solvents (n-hexane, ethyl acetate and n-butanol) to afford the corresponding fractions and water residue. Among them, the EtOAc-soluble portion was subjected to medium pressure liquid chromatography (MPLC) over a reversed-phase SiO2 column to give compound 1. The isolated compound was identified based on the proton and carbon nuclear magnetic resonance (NMR) spectra. The release of nitric oxide, prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 secreted by mouse macrophages was measured using RAW264.7 cell culture supernatant.Results: Shiranuhi (Korean name, Hallabong) is an important citrus species cultivated in Jeju Island, Korea. A polymethoxyflavonoid (PMF), tetramethyl-O-scutellarin (1), was isolated from the peels of immature Shiranuhi fruit. Upon the evaluation of anti-inflammatory effects, the flavonoid 1 decreased the nitric oxide production in macrophage cells with high efficiency, viz, 50 % inhibition concentration, IC50 of 57.4 μM. Subsequent studies demonstrated that PMF 1 effectively inhibited the generation of PGE2, TNF-α, IL-1β, and IL-6 cytokine in a dose-dependent manner.Conclusion: Tetramethyl-O-scutellarin (1) has been successfully isolated from Shiranuhi species for the first time. Thus, Shiranuhi fruit peel extract containing PMF 1 can potentially be applied as an antiinflammatory ingredient in food or cosmetic industries.Keywords: Shiranuhi fruit, Nitric oxide, Tetramethyl-O-scutellarin, Anti-inflammator

Age-dependent resistance of a perennial herb, Aristolochia contorta against specialist and generalist leaf-chewing herbivores

Plants need to balance investments in growth and defense throughout their life to increase their fitness. To optimize fitness, levels of defense against herbivores in perennial plants may vary according to plant age and season. However, secondary plant metabolites often have a detrimental effect on generalist herbivores, while many specialists have developed resistance to them. Therefore, varying levels of defensive secondary metabolites depending on plant age and season may have different effects on the performance of specialist and generalist herbivores colonizing the same host plants. In this study, we analyzed concentrations of defensive secondary metabolites (aristolochic acids) and the nutritional value (C/N ratios) of 1st-, 2nd- and 3rd-year Aristolochia contorta in July (the middle of growing season) and September (the end of growing season). We further assessed their effects on the performances of the specialist herbivore Sericinus montela (Lepidoptera: Papilionidae) and the generalist herbivore Spodoptera exigua (Lepidoptera: Noctuidae). Leaves of 1st-year A. contorta contained significantly higher concentrations of aristolochic acids than those of older plants, with concentrations tending to decrease over the first-year season. Therefore, when first year leaves were fed in July, all larvae of S. exigua died and S. montela showed the lowest growth rate compared to older leaves fed in July. However, the nutritional quality of A. contorta leaves was lower in September than July irrespective of plant age, which was reflected in lower larval performance of both herbivores in September. These results suggest that A. contorta invests in the chemical defenses of leaves especially at a young age, while the low nutritional value of leaves seems to limit the performance of leaf-chewing herbivores at the end of the season, regardless of plant age

Pregnancy-related knowledge, risk perception, and reproductive decision making of women with epilepsy in Korea

AbstractPurposeTo determine the influence of pregnancy-related knowledge and the risk perception on reproductive decision making in women with epilepsy.MethodsWe enrolled women with epilepsy, who were of reproductive age and were considering having children in the future. A questionnaire was used to assess the level of pregnancy-related knowledge, perception of the offspring's risk for developing epilepsy or for having a congenial anomaly, and discussion with a physician concerning pregnancy-related issues. We evaluated the following outcome variables: (1) the decision to discontinue anti-epileptic drug (AED) during a future pregnancy regardless of the medical indication; and (2) the decision to have fewer children because of epilepsy.ResultsWe enrolled a total of 186 women with epilepsy. (1) Fifty-eight percent of the women were considering discontinuing AED during a future pregnancy regardless of the medical indication, and 25% of the women decided to have fewer children because of epilepsy. (2) The decision to discontinue AED during a future pregnancy was associated with low-level pregnancy-related knowledge. (3) The decision to have fewer children because of epilepsy was associated with an exaggerated perception of the offspring's risk for developing epilepsy. (4) The women who had ever discussed pregnancy-related issues with their physician were less likely to decide to discontinue AED during a future pregnancy; however, a discussion on this issue had no impact on their decision to have fewer children because of epilepsy.ConclusionMore than 50% of the women would decide to discontinue AED during a future pregnancy, and 25% of the women stated that they would have fewer children because of epilepsy. These data highlight the importance of education on pregnancy-related issues and genetic risk counseling

Efficient Photoelectrochemical Water Oxidation by Metal-Doped Bismuth Vanadate Photoanode with Iron Oxyhydroxide Electrocatalyst

Intensive attention has been currently focused on the discovery of semiconductor and proficient cocatalysts for eventual applications to the photoelectrochemical water splitting system. A W-Mo-doped BiVO4 semiconductor was prepared by the surfactant-assisted thermal decomposition method on a fluorine-doped tin oxide conductive film. The W-Mo-doped BiVO4 films showed a porous morphology with the grain sizes of about 270 nm. Because the hole diffusion length of BiVO4 is about 100 nm, the W-Mo-doped BiVO4 film in this study is an ideal candidate for the photoelectrochemical water oxidation. Iron oxyhydroxide (FeOOH) electrocatalyst was chemically deposited on the W-Mo-doped BiVO4 to investigate the effect of the electrocatalyst on the semiconductor. The W-Mo-doped BiVO4/FeOOH composite electrode showed enhanced activity compared to the pristine W-Mo-doped BiVO4 electrode for water oxidation reaction. The chemical deposition is a promising method for the deposition of FeOOH on semiconductor

Comparison of Rapid Diagnostic Tests for the Detection of Plasmodium vivax Malaria in South Korea

South Korea is one of many countries with endemic Plasmodium vivax malaria. Here we report the evaluation of four rapid diagnostic tests (RDTs) for diagnosis of this disease. A total of 253 subjects were enrolled in the study. The sensitivities, specificities and agreement frequencies were estimated by comparing the four RDTs against the standard of nested-PCR and microscopic examination. The CareStartTM and SD Bioline had higher test sensitivities (99.4 and 98.8%, respectively) compared with the NanoSign and Asan Easy tests (93.0 and 94.7%, respectively). The CareStartTM and SD Bioline tests could detect P. vivax in samples with parasite densities <150/μl, which was a slightly better performance than the other two RDTs. The quantitative accuracy of the four RDTs was also estimated by comparing results with P. vivax counts from blood samples. Lower test price would result in increased use of these RDTs in the field. The results of this study contribute valuable information that will aid in the selection of a diagnostic method for the detection of malaria