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

The EPOCH Project: I. Periodic variable stars in the EROS-2 LMC database

The EPOCH (EROS-2 periodic variable star classification using machine learning) project aims to detect periodic variable stars in the EROS-2 light curve database. In this paper, we present the first result of the classification of periodic variable stars in the EROS-2 LMC database. To classify these variables, we first built a training set by compiling known variables in the Large Magellanic Cloud area from the OGLE and MACHO surveys. We crossmatched these variables with the EROS-2 sources and extracted 22 variability features from 28 392 light curves of the corresponding EROS-2 sources. We then used the random forest method to classify the EROS-2 sources in the training set. We designed the model to separate not only $\delta$ Scuti stars, RR Lyraes, Cepheids, eclipsing binaries, and long-period variables, the superclasses, but also their subclasses, such as RRab, RRc, RRd, and RRe for RR Lyraes, and similarly for the other variable types. The model trained using only the superclasses shows 99% recall and precision, while the model trained on all subclasses shows 87% recall and precision. We applied the trained model to the entire EROS-2 LMC database, which contains about 29 million sources, and found 117 234 periodic variable candidates. Out of these 117 234 periodic variables, 55 285 have not been discovered by either OGLE or MACHO variability studies. This set comprises 1 906 $\delta$ Scuti stars, 6 607 RR Lyraes, 638 Cepheids, 178 Type II Cepheids, 34 562 eclipsing binaries, and 11 394 long-period variables. A catalog of these EROS-2 LMC periodic variable stars will be available online at http://stardb.yonsei.ac.kr and at the CDS website (http://vizier.u-strasbg.fr/viz-bin/VizieR).Comment: 18 pages, 20 figures, suggseted language-editing by the A&A editorial office is applie

Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer

AbstractUsing the planar lipid bilayer technique, we tested whether NO directly activates calcium-activated potassium (Maxi-K) channels isolated from rat brain. We used streptozotocin (STZ) as NO donor, and the NO release was controlled with light. In the presence of 100–800 μM STZ, the Maxi-K channel activity increased up to 3-fold within several tens of seconds after the light was on, and reversed to the control level several minutes after shutting off the light. Similar activation was observed with other NO donors such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside. The degree of activity increase was dependent upon the initial open probability (Pinit). When the Pinit was lower, the activity increase was greater. These results demonstrate that NO can directly affect the Maxi-K channel activity, and suggest that the Maxi-K channel might be one of the physiological targets of NO in brain

Detecting Variability in Massive Astronomical Time-series Data. II. Variable Candidates in the Northern Sky Variability Survey

We present variability analysis of data from the Northern Sky Variability Survey (NSVS). Using the clustering method, which defines variable candidates as outliers from large clusters, we cluster 16,189,040 light curves having data points at more than 15 epochs as variable and non-variable candidates in 638 NSVS fields. Variable candidates are selected depending on how strongly they are separated from the largest cluster and how rarely they are grouped together in eight-dimensional space spanned by variability indices. All NSVS light curves are also cross-correlated with IRAS , AKARI, Two Micron All Sky Survey, Sloan Digital Sky Survey (SDSS), and GALEX objects, as well as known objects in the SIMBAD database. The variability analysis and cross-correlation results are provided in a public online database, which can be used to select interesting objects for further investigation. Adopting conservative selection criteria for variable candidates, we find about 1.8 million light curves as possible variable candidates in the NSVS data, corresponding to about 10% of our entire NSVS sample. Multi-wavelength colors help us find specific types of variability among the variable candidates. Moreover, we also use morphological classification from other surveys such as SDSS to suppress spurious cases caused by blending objects or extended sources due to the low angular resolution of the NSVS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98631/1/1538-3881_143_3_65.pd

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJI

In Vivo

Platycodin D is a major pharmacological constituent of Platycodi radix and has showed various pharmacological activities through oxidative stress defense mechanisms. Here, possible antitumor, anticachexia, and immunomodulatory activities of platycodin D were observed on the H520 tumor cell-bearing athymic nude mice after confirming the in vitro cytotoxicity. Platycodin D was orally administered at dose levels of 200, 100, and 50 mg/kg, once a day for 35 days from 15 days after implantation. The results were compared with gemcitabine 160 mg/kg intraperitoneally treated mice (7-day intervals). Platycodin D showed favorable cytotoxic effects on the H520 cells, and also dose-dependently decreased the tumor volumes and weights with increases of apoptotic cells (caspase-3 and PARP immunopositive cells), iNOS and TNF-α immunoreactivities, decreases of COX-2 immunoreactivities in tumor masses. Platycodin D also showed dose-dependent immunostimulatory and anticachexia effects. Gemcitabine showed favorable cytotoxity against H520 tumor cell and related in vivo antitumor effects but aggravated the cancer related cachexia and immunosuppress in H520 tumor cell-bearing athymic nude mice. Taken together, it is considered that oral treatment of platycodin D has potent antitumor activities on H520 cells through direct cytotoxic effects, increases of apoptosis in tumor cells, and immunostimulatory effects and can be control cancer related cachexia