Unoxidized graphene/alumina nanocomposite: fracture- and wear-resistance effects of graphene on alumina matrix.

It is of critical importance to improve toughness, strength, and wear-resistance together for the development of advanced structural materials. Herein, we report on the synthesis of unoxidized graphene/alumina composite materials having enhanced toughness, strength, and wear-resistance by a low-cost and environmentally benign pressure-less-sintering process. The wear resistance of the composites was increased by one order of magnitude even under high normal load condition (25 N) as a result of a tribological effect of graphene along with enhanced fracture toughness (KIC) and flexural strength (σf) of the composites by ~75% (5.60 MPa·m(1/2)) and ~25% (430 MPa), respectively, compared with those of pure Al2O3. Furthermore, we found that only a small fraction of ultra-thin graphene (0.25-0.5 vol%, platelet thickness of 2-5 nm) was enough to reinforce the composite. In contrast to unoxidized graphene, graphene oxide (G-O) and reduced graphene oxide (rG-O) showed little or less enhancement of fracture toughness due to the degraded mechanical strength of rG-O and the structural defects of the G-O composites.

Effect of La2O3 addition on interface chemistry between 4YSZ top layer and Ni based alloy bond coat in thermal barrier coating by EB PVD.

The effect of a 5 mol% La2O3 addition on the forming behavior and compositional variation at interface between a 4 mol% Yttria (Y2O3) stabilized ZrO2 (4YSZ) top coat and bond coat (NiCrAlY) as a thermal barrier coating (TBC) has been investigated. Top coats were deposited by electron beam physical vapor deposition (EB PVD) onto a super alloy (Ni-Cr-Co-Al) substrate without pre-oxidation of the bond coat. Top coats are found to consist of dense columnar grains with a thin interdiffusion layer between metallic bond coats. In the as-received 4YSZ coating, a thin interdiffusion zone at the interface between the top and bond coats was found to consist of a Ni-Zr intermetallic compound with a reduced quantity of Y, Al or O elements. On the other hand, in the case of an interdiffusion area of 5 mol% La2O3-added 4YSZ coating, it was found that the complicated composition and structure with La-added YSZ and Ni-Al rich compounds separately. The thermal conductivity of 5 mol% La2O3-added 4YSZ coating (- 1.6 W/m x k at 1100 degrees C) was lower than a 4YSZ coating (- 3.2 W/m x k at 1100 degrees C) alone.

Endogenous stromal cell-derived factor-1 (CXCL12) supports autonomous growth of acute myeloid leukemia cells.

We investigated the role of endogenous stromal cell-derived factor-1 (SDF-1; CXCL12) in the survival and proliferation of acute myeloid leukemia (AML) cells in vitro. CD34(+) cells from the peripheral blood of five patients with AML, as well as five AML cell lines, produced and secreted SDF-1. Knock-down of endogenous SDF-1 expression using siRNA technology downregulated the constitutive phosphorylation of SDF-1-related signaling molecules and significantly inhibited spontaneous proliferation of the AML cell lines during a 3-day incubation in serum-free conditions. These results indicate that endogenous SDF-1 expression by AML cells plays a role in the autonomous growth of the cells.

Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α.

Given the important role of CXCR4 in cancer metastasis, microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion. Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior. CXCR4 is upregulated in several cancer cells under hypoxic conditions, suggesting a relationship between tumor hypoxia and CXCR4. However, the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood. KATO III gastric cancer cells were exposed to hypoxia or normoxia. CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry. Wound healing, migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12, a major CXCR4 ligand. CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATO III cells following exposure to hypoxia. This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses (migration and invasion) to CXCL12 treatment in vitro. The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA. Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner, and that upregulation of CXCR4 plays a role in cancer cell migration and invasion. Thus, disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer.

Expression of stromal cell-derived factor-1α is an independent risk factor for lymph node metastasis in early gastric cancer.

Lymph node metastasis is considered to be a significant prognostic factor for early gastric cancer (EGC). However, no real consensus exists on which patient and/or tumor characteristics are associated with lymph node metastasis. We investigated whether stromal cell-derived factor (SDF)-1α expression correlates with lymph node metastasis in patients with EGC by immunohistochemically examining the expression of SDF-1α in 138 archival tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were grouped into SDF-1α-positive and SDF-1α-negative groups, respectively. No significant differences existed with respect to age, gender, tumor location, proportion of tumors >20 mm in size, macroscopic type, depth of invasion or histology between the SDF-1α-positive and -negative groups. However, the SDF-1α-positive group was significantly correlated with lymphovascular invasion and lymph node metastasis. Results of the univariate analyses indicated that lymphovascular invasion, undifferentiated histology and SDF-1α positivity were statistically significant risk factors affecting lymph node metastasis in patients with EGC. Multivariate analyses showed that lymphovascular invasion [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009], undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF-1α positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent risk factors predicting lymph node metastasis in EGC. In conclusion, these results suggest that SDF-1α expression in tumor cells is a predictive marker of lymph node metastasis in EGC.

Evaluation of the combined expression of chemokine SDF-1α and its receptor CXCR4 as a prognostic marker for gastric cancer.

Chemokine stromal cell-derived factor (SDF)-1α and its receptor CXC chemokine receptor 4 (CXCR4) have been shown to impact cancer progression. Accumulating evidence suggests that CXCR4 and SDF-1α expression is useful for evaluating the risk of gastric cancer progression. Thus, combined analysis of SDF-1α and CXCR4 should have high prognostic potential as a molecular marker for gastric cancer. We investigated the expression of SDF-1α and CXCR4 using immunohistochemistry in relation to prognosis, clinicopathological features and clinical outcomes in 221 cases of primary gastric cancer. Patients were categorized into three groups according to CXCR4 and SDF-1α expression: high CXCR4/high SDF-1α, low CXCR4/low SDF-1α, and high CXCR4/low SDF-1α - low CXCR4/high SDF-1α. No significant differences were noted in age, gender, histology, tumor location, lymphovascular invasion or proportion of tumor size >5 cm among the three groups. However, high CXCR4/high SDF-1α expression in tumor cells was significantly associated with depth of invasion of the tumor, lymph node involvement, and higher tumor stage compared to tumors with low CXCR4/low SDF-1α expression or high CXCR4/low SDF-1α - low CXCR4/high SDF-1α expression. Furthermore, patients with high CXCR4/high SDF-1α expression had the worst patient prognosis, whereas patients who had low CXCR4/low SDF-1α expression showed the most favorable prognosis. In conclusion, CXCR4 and SDF-1α are useful prognostic factors in gastric cancer, and the combination of high CXCR4 protein expression with high SDF-1α expression suggests a dismal prognosis.

Differential effects of CXCR4 antagonists on the survival and proliferation of myeloid leukemia cells in vitro.

BACKGROUND: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. METHODS: The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34(+) cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. RESULTS: AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10(-5) M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. CONCLUSION: The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.

Use of cold dry air provocation with acoustic rhinometry in detecting nonspecific nasal hyperreactivity.

BACKGROUND: Cold dry air provocation is useful for evaluating nonspecific nasal hyperreactivity. However, there is no research on nasal volume and dimensions after cold dry air provocation. In this respect, acoustic rhinometry is a useful tool in objectively assessing nasal cavity volume and dimension. The goal of this study was to evaluate nonspecific hyperreactivity using cold dry air provocation with acoustic rhinometry. METHODS: Cold dry air provocation with acoustic rhinometry was performed on 21 healthy volunteers (group A), 24 patients with allergic rhinitis (group B), and 32 patients with nonallergic rhinitis (group C). The change in symptoms using a visual analog scale (VAS), amount of rhinorrhea, and change of total nasal volume (TNV) and minimal cross-sectional area (MCA) were measured in all three groups. RESULTS: The two patient groups showed greater change in nasal symptoms (VAS, 2.0 +/- 2.3 in group C versus 0.9 +/- 1.8 in group A), more rhinorrhea (0.4 +/- 0.7 g in group B and 0.3 +/- 0.3 g in group C versus 0.1 +/- 0.1 g in group A), and greater change in total nasal volume (TNV) and MCA. The patient group with history of nonspecific hyperreactivity showed more rhinorrhea (0.5 +/- 0.7 g versus 0.1 +/- 0.2 g) and greater change in TNV and MCA (TNV, 56.8 +/- 39.5% versus 18.0 +/- 17.0%; MCA, 86.6 +/- 81.0% versus 11.5 +/- 9.7%). CONCLUSION: Cold dry air provocation with acoustic rhinometry could be a useful adjunct tool for detecting nonspecific hyperreactivity.