Prediction and identification of synergistic compound combinations against pancreatic cancer cells.

Resistance to current therapies is common for pancreatic cancer and hence novel treatment options are urgently needed. In this work, we developed and validated a computational method to select synergistic compound combinations based on transcriptomic profiles from both the disease and compound side, combined with a pathway scoring system, which was then validated prospectively by testing 30 compounds (and their combinations) on PANC-1 cells. Some compounds selected as single agents showed lower GI50 values than the standard of care, gemcitabine. Compounds suggested as combination agents with standard therapy gemcitabine based on the best performing scoring system showed on average 2.82-5.18 times higher synergies compared to compounds that were predicted to be active as single agents. Examples of highly synergistic in vitro validated compound pairs include gemcitabine combined with Entinostat, thioridazine, loperamide, scriptaid and Saracatinib. Hence, the computational approach presented here was able to identify synergistic compound combinations against pancreatic cancer cells

Room-temperature ferromagnetic properties in Mn-doped rutile TiO 2Àd thin films

Abstract Room-temperature ferromagnetic properties of Mn-doped reduced titanium dioxide ðTi 1Àx Mn x O 2Àd Þ thin films with rutile structure synthesized by a sol-gel method have been detected for a limited range of Mn composition ðxÞ. The Ti 1Àx Mn x O 2Àd films were found to be p-type semiconducting with hole concentration near 10 19 cm À3 . The observed ferromagnetism in the Ti 1Àx Mn x O 2Àd films is not related to the hole concentration but related to x. The room-temperature ferromagnetism is attributable to magnetic polaron formed by trapped electron in oxygen vacancy and magnetic ions around it. Thus, the existence of oxygen vacancies is necessary for the room-temperature ferromagnetism.

Interferometric Fiber Optic Sensors

Fiber optic interferometers to sense various physical parameters including temperature, strain, pressure, and refractive index have been widely investigated. They can be categorized into four types: Fabry-Perot, Mach-Zehnder, Michelson, and Sagnac. In this paper, each type of interferometric sensor is reviewed in terms of operating principles, fabrication methods, and application fields. Some specific examples of recently reported interferometeric sensor technologies are presented in detail to show their large potential in practical applications. Some of the simple to fabricate but exceedingly effective Fabry-Perot interferometers, implemented in both extrinsic and intrinsic structures, are discussed. Also, a wide variety of Mach-Zehnder and Michelson interferometric sensors based on photonic crystal fibers are introduced along with their remarkable sensing performances. Finally, the simultaneous multi-parameter sensing capability of a pair of long period fiber grating (LPG) is presented in two types of structures; one is the Mach-Zehnder interferometer formed in a double cladding fiber and the other is the highly sensitive Sagnac interferometer cascaded with an LPG pair

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways.

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of CXCL8, CYR61, FGF16 and FGFRL1 was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation via the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, via ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects

Influence of Lactate Dehydrogenase and Cyclosporine A Level on the Incidence of Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor

Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease

Fabrazyme has been widely used for treatment of Fabry disease since its approval by the U.S. Food and Drug Administration in 2003. This study was undertaken to assess the short-term efficacy and safety of enzyme replacement therapy (ERT) for Fabry disease in Korea. Eight male patients and three female symptomatic carriers aged 13 to 48 yr were included. Fabrazyme was administered by intravenous infusion at a dose of 1 mg/kg every 2 weeks. Plasma and urine globotriaosylceramide (GL-3) levels, serum creatinine, creatinine clearance, and 24-hr urine protein levels were measured every 3 months. Kidney biopsies, ophthalmologic exams, and pure tone audiometry were performed before and 1 yr after ERT. Kidney function, including serum creatinine, creatinine clearance, and the 24-hr urine protein level, remained stable during ERT. Plasma and urine GL-3 levels were reduced within 3 to 6 months of ERT initiation. Microvascular endothelial deposits of GL-3 were decreased from renal biopsy specimens after 1 yr of treatment. The severity of sensorineural hearing loss and tinnitus did not improve after ERT. ERT is safe and effective in stabilizing renal function and clearing microvascular endothelial GL-3 from kidney biopsy specimen in Korean patients with Fabry disease

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma

BACKGROUND: The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC). METHODS: Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists. RESULTS: There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3. CONCLUSIONS: The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.This study was partly supported by research fund of Chungnam National University in 2007

Acupuncture for dry eye: a multicentre randomised controlled trial with active comparison intervention (artificial tear drop) using a mixed method approach protocol

<p>Abstract</p> <p>Background</p> <p>Previous studies of acupuncture show favourable results for both subjective and objective outcomes of dry eye. However, firm conclusions could not be drawn from these studies because the quality of the trials was too low to establish concrete evidence. Therefore, this study was designed both to avoid the flaws of the existing trials and to assess the effectiveness, cost-effectiveness and qualitative characteristics of acupuncture treatment for dry eye.</p> <p>Methods/design</p> <p>One hundred fifty participants with dry eye will be recruited into three independent hospitals from different areas: Korea Institute of Oriental Medicine, DongGuk University Ilsan Oriental Hospital and Dongshin University Gwangju Oriental Hospital. The number of participants required was calculated from the data of a previous, relevant study. These patients will be randomly allocated into acupuncture treatment or artificial tear groups. Either 17 acupuncture points (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) will be used 3 times a week or disposable artificial tear drops (Refresh Plus^®, ALLERGAN) will be provided for use at least once a day for 4 weeks. The ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer I test, visual analogue scale (VAS) for self-assessment of ocular discomfort, general assessment (by both acupuncture practitioners and participants) and quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2 (MYMOP-2) will be assessed for approximately 3-months for each study participant. In addition, qualitative study and cost-effectiveness of acupuncture treatment will be conducted.</p> <p>Trial registration</p> <p>ClinicalTrials.gov (Identifier: NCT01105221).</p