Co-administration of vismodegib with rosiglitazone or combined oral contraceptive in patients with locally advanced or metastatic solid tumors: a pharmacokinetic assessment of drug-drug interaction potential.

Purpose: Vismodegib, a first-in-class oral hedgehog pathway inhibitor, is an effective treatment for advanced basal cell carcinoma. Based on in vitro data, a clinical drug-drug interaction (DDI) assessment of cytochrome P450 (CYP) 2C8 was necessary; vismodegib's teratogenic potential warranted a DDI study with oral contraceptives (OCs).

Methods: This single-arm, open-label study included two cohorts of patients with locally advanced or metastatic solid malignancies [Cohort 1: rosiglitazone 4 mg (selective CYP2C8 probe); Cohort 2: OC (norethindrone 1 mg/ethinyl estradiol 35 μg; CYP3A4 substrate)].

Structural characterization and radioprotection of bone marrow hematopoiesis of two novel polysaccharides from the root of Angelica sinensis (Oliv.) Diels.

Two novel homogeneous polysaccharides, APS-1a and APS-3a were successfully isolated from the root of Angelica sinensis. APS-1a was composed of galactose, arabinose and glucose in a relatively molar percentage of 57.34%, 27.

pH-induced outward movement of star centers within coumarin-centered star-block polymer micelles.

A novel coumarin-centered amphiphilic star-block polymer of C-(PDMAEMA(80)-b-PS(8))(3) has been designed to investigate the pH-induced accompanying outward movement of hydrophobic coumarin centers within the polymer micelles upon protonation.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

Background: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure.

Association between single nucleotide polymorphisms in ERCC4 and risk of squamous cell carcinoma of the head and neck.

Background: Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer susceptibility.

Methodology/principal Findings: In this case-control study, we evaluated associations of four selected potentially functional SNPs in ERCC4 with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non-Hispanic white patients with SCCHN and 1,046 cancer-free matched controls.

Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer.

Caspase-8 and caspase-10 play crucial roles in both cancer development and chemotherapy efficacy. In this study, we aimed to comprehensively assess single nucleotide polymorphisms (SNPs) of the caspase-8 (CASP8) and caspase-10 (CASP10) genes in relation to toxicity outcomes with first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 13 tag SNPs of CASP8 and CASP10 in 663 patients with advanced NSCLC treated with platinum-based chemotherapy regimens.

Interface driven energy filtering of thermoelectric power in spark plasma sintered Bi(2)Te(2.7)Se(0.3) nanoplatelet composites.

Control of competing parameters such as thermoelectric (TE) power and electrical and thermal conductivities is essential for the high performance of thermoelectric materials. Bulk-nanocomposite materials have shown a promising improvement in the TE performance due to poor thermal conductivity and charge carrier filtering by interfaces and grain boundaries. Consequently, it has become pressingly important to understand the formation mechanisms, stability of interfaces and grain boundaries along with subsequent effects on the physical properties.

[Chondrogenic phenotype differentiation of bone marrow mesenchymal stem cells induced by bone morphogenetic protein 2 under hypoxic microenvironment in vitro].

Objective: To investigate the role of bone morphogenetic protein 2 (BMP-2) combined with hypoxic microenvironment in chondrogenic phenotype differentiation of bone marrow mesenchymal stem cells (BMSCs) of rat in vitro.

Methods: BMSCs were harvested from 4-week-old female Sprague Dawley rats. BMSCs at passage 2 were divided into 4 groups according different culture conditions: normoxia control group (group A), normoxia and BMP-2 group (group B), hypoxia control group (3% oxygen, group C), and hypoxia and BMP-2 group (group D).

Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice.

Limping gait improvement by femoral lengthening in ankylotic hips and limb length discrepancy in young adults.

Objective: To investigate the clinical improvement of limping gait in patients with ankylotic hips and limb length discrepancy.

Methods: From 1996 to 2005, 12 patients with ankylotic hips and limb length discrepancy were treated by distraction osteogenesis with a mono-lateral external fixator and an intramedullary nail. The limb length discrepancy was 6.

Association study of polymorphisms in the cyclooxygenase-2 gene and Alzheimer's disease risk in Chinese.

To determine if polymorphisms (-765G/C, -1195G/A and 8473T/C) of the cyclooxygenase-2 (COX-2) gene can be associated with Alzheimer disease (AD). The frequency of the polymorphisms was determined in 244 cases and 226 controls. The results revealed that the distributions of COX-2 -765G/C and 8473T/C polymorphisms were statistically not significant between AD cases and controls.

Incorporating single-nucleotide polymorphisms into the Lyman model to improve prediction of radiation pneumonitis.

Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-β, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC).

Methods And Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGFβ, TNFα, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade≥3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors.

Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy.

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (-460 T > C [rs833061], -634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP ≥grade 3) in 195 NSCLC patients.

β-amyloid42 induces desensitization of CXC chemokine receptor-4 via formyl peptide receptor in neural stem/progenitor cells.

The deposition of β-amyloid (Aβ) plaques and progressive loss of neurons are two main characteristics of Alzheimer's disease (AD). Supplement of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the neurodegenerative diseases. However, hostile microenvironment of neurodegenerative brain is harmful for the neuroregeneration.

Developing implantable neuroprosthetics: a new model in pig.

A new model has been established in the domestic pig for neural prosthetic device development and testing. To this end, we report on a complete neural prosthetic developmental system using a wireless sensor as the implant, a pig as the animal model, and a novel data acquisition paradigm for actuator control. A new type of stereotactic frame with clinically-inspired fixations pins that place the pig brain in standard surgical plane was developed and tested with success during the implantation of the microsystem.

A 32-channel fully implantable wireless neurosensor for simultaneous recording from two cortical regions.

We present a fully implantable, wireless, neurosensor for multiple-location neural interface applications. The device integrates two independent 16-channel intracortical microelectrode arrays and can simultaneously acquire 32 channels of broadband neural data from two separate cortical areas. The system-on-chip implantable sensor is built on a flexible Kapton polymer substrate and incorporates three very low power subunits: two cortical subunits connected to a common subcutaneous subunit.

[Effects of telmisartan on nonalcoholic steatohepatitis rat model by activating peroxisome proliferator-activated receptor r].

To investigate the effects of telmisartan on steatohepatitis (NASH) in rats by activating peroxisome proliferator-activated receptor gamma (r). Thirty male SD rats were randomized into normal control group, NASH control group and telmisartan prevention group. Normal control group was given standard food and the other two groups were given high fat diet for 16 weeks to induce NASH.

Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to endometrial cancer and clinical outcomes.

Purpose: The phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mTOR and Ras/Raf/MEK/ERK pathways have been implicated in endometrial tumorigenesis. In this candidate pathway analysis, we investigated associations between genetic variations in these two pathways and both risk and clinical outcomes of endometrial cancer.

Methods: We genotyped a total of 48 potentially functional SNPs in 11 key genes (AKT1, AKT2, AKT3, BRAF, FRAP1, KRAS, PDPK1, PIK3CA, PIK3CB, PIK3R1, and PTEN) with the Sequenom genotyping platform in 115 endometrial cancer patients and 230 cancer-free women to evaluate their associations with risk, survival, and recurrence of endometrial cancer.

Overexpression of 5-lipoxygenase increases the neuronal vulnerability of PC12 cells to Aβ₄₂.

5-Lipoxygenase (5-LOX), which is believed to be a major source of oxidative stress, participates in somatostatin-receptor transmembrane signaling in the central nervous system. We used the Tet-On inducible expression system in PC12 cells to obtain cell lines with reproducible, stable 5-LOX expression levels to study its function. Cell apoptosis rates induced by Aβ(42) were determined using an apo-BrdDU kit.

Association between PARP-1 V762A polymorphism and cancer susceptibility: a meta-analysis.

Poly(ADP-ribose) polymerase-1 (PARP-1 catalyzes poly(ADP-ribosyl)ation to various proteins involved in many cellular processes, including DNA damage detection and repair and cell proliferation and death. PARP-1 has been implicated in human carcinogenesis, but the association between the most-studied PARP-1 V762A polymorphism (rs1136410) and risk of various cancers was reported with inconclusive results. The aim of this study was to assess the association between the PARP-1 V762A polymorphism and cancer risk.