Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting Heat Shock Protein 90 Expression

Purpose: To investigate whether curcumin augments bortezomib-induced apoptosis in myeloma cells (MM1.R line), and to explore the molecular mechanism with regard to heat shock protein 90 (HSP90) expression.Methods: MTT cell viability assay was used to assess growth inhibition of MM1.R cells at different concentrations of curcumin alone and also combined with 0.01 mM bortezomib. Annexin V and propidium iodide (PI) labeling were used to detect apoptosis. Caspase 3, caspase 9, NF-κB, and HSP 90 protein expression were measured by Western blotting.Results: Curcumin alone inhibited MM1.R cell growth and increased apoptosis in a concentration dependent manner. When curcumin was combined with low concentration (0.01 mM) bortezomib, both effects（viability inhibition and apoptosis induction increased (p < 0.05), whereas bortezomib alone had no effect (p > 0.05). Western blotting revealed that for curcumin and combined treatments, expression of the apoptotic markers, caspase 3 and caspase 9, increased while expression of NF-κB and HSP 90 decreased (p < 0.05). Again, low concentration bortezomib alone had no effect, whereas the combined treatment showed the largest effect, thus suggesting that the actions of curcumin and bortezomib are synergistic.Conclusion: Curcumin increased MM1.R cell sensitivity to bortezomib, which may be due to suppression of NF-κB and HSP90 activity.Keywords: Curcumin, Bortezomib, Myeloma cells, Cell growth, Apoptosis, Heat shock protein 9

MicroRNA expression, survival, and response to interferon in liver cancer

BACKGROUND: Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. METHODS: We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase-polymerase- chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. RESULTS: In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor κB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. CONCLUSIONS: The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa. Copyright © 2009 Massachusetts Medical Society. All rights reserved.published_or_final_versio

Effect of Size-Dependent Thermal Instability on Synthesis of Zn2 SiO4-SiOx Core–Shell Nanotube Arrays and Their Cathodoluminescence Properties

Vertically aligned Zn2SiO4-SiOx(x < 2) core–shell nanotube arrays consisting of Zn2SiO4-nanoparticle chains encapsulated into SiOx nanotubes and SiOx-coated Zn2SiO4 coaxial nanotubes were synthesized via one-step thermal annealing process using ZnO nanowire (ZNW) arrays as templates. The appearance of different nanotube morphologies was due to size-dependent thermal instability and specific melting of ZNWs. With an increase in ZNW diameter, the formation mechanism changed from decomposition of “etching” to Rayleigh instability and then to Kirkendall effect, consequently resulting in polycrystalline Zn2SiO4-SiOx coaxial nanotubes, single-crystalline Zn2SiO4-nanoparticle-chain-embedded SiOx nanotubes, and single-crystalline Zn2SiO4-SiOx coaxial nanotubes. The difference in spatially resolved optical properties related to a particular morphology was efficiently documented by means of cathodoluminescence (CL) spectroscopy using a middle-ultraviolet emission at 310 nm from the Zn2SiO4 phase

Hollow Sodium Tungsten Bronze (Na0.15WO3) Nanospheres: Preparation, Characterization, and Their Adsorption Properties

We report herein a facile method for the preparation of sodium tungsten bronzes hollow nanospheres using hydrogen gas bubbles as reactant for chemical reduction of tungstate to tungsten and as template for the formation of hollow nanospheres at the same time. The chemical composition and the crystalline state of the as-prepared hollow Na0.15WO3nanospheres were characterized complementarily, and the hollow structure formation mechanism was proposed. The hollow Na0.15WO3nanospheres showed large Brunauer–Emment–Teller specific area (33.8 m2 g−1), strong resistance to acids, and excellent ability to remove organic molecules such as dye and proteins from aqueous solutions. These illustrate that the hollow nanospheres of Na0.15WO3should be a useful adsorbent

Prolate spheroidal hematite particles equatorially belt with drug-carrying layered double hydroxide disks: Ring Nebula-like nanocomposites

A new nanocomposite architecture is reported which combines prolate spheroidal hematite nanoparticles with drug-carrying layered double hydroxide [LDH] disks in a single structure. Spindle-shaped hematite nanoparticles with average length of 225 nm and width of 75 nm were obtained by thermal decomposition of hydrothermally synthesized hematite. The particles were first coated with Mg-Al-NO3-LDH shell and then subjected to anion exchange with salicylate ions. The resulting bio-nanohybrid displayed a close structural resemblance to that of the Ring Nebula. Scanning electron microscope and transmission electron microscopy images showed that the LDH disks are stacked around the equatorial part of the ellipsoid extending along the main axis. This geometry possesses great structural tunability as the composition of the LDH and the nature of the interlayer region can be tailored and lead to novel applications in areas ranging from functional materials to medicine by encapsulating various guest molecules

Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival

Abstract Background The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival. Methods Tumor tissue from HCC patients with (n = 43) and without (n = 138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays. Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression, in bone metastasis. Patient survival was analyzed by Kaplan-Meier curves and log-rank tests. Results CXCR4 overexpression was detected in 34 of 43 (79.1%) patients with bone metastases and in 57 of 138 (41.3%) without bone metastases. CXCR4 expression correlated with (correlation coefficient: 0.551, P predictive of HCC bone metastases (AUC: 0.689; 95%CI: 0.601 – 0.776; P ). CXCR4 staining intensity correlated with the bone metastasis-free survival (correlation coefficient: -0.359; P = 0.018). CXCR4 overexpression in primary tumors (n = 91) decreased overall median survival (18.0 months vs. 36.0 months, P 0.001). Multivariable analysis identified CXCR4 as a strong, independent risk factor for reduced disease-free survival (relative risk [RR]: 5.440; P = 0.023) and overall survival (RR: 7.082; P = 0.001). Conclusion CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome.</p

Template Route to Chemically Engineering Cavities at Nanoscale: A Case Study of Zn(OH)2 Template

A size-controlled Zn(OH)2 template is used as a case study to explain the chemical strategy that can be executed to chemically engineering various nanoscale cavities. Zn(OH)2 octahedron with 8 vertices and 14 edges is fabricated via a low temperature solution route. The size can be tuned from 1 to 30 μm by changing the reaction conditions. Two methods can be selected for the hollow process without loss of the original shape of Zn(OH)2 template. Ion-replacement reaction is suitable for fabrication of hollow sulfides based on the solubility difference between Zn(OH)2 and products. Controlled chemical deposition is utilized to coat an oxide layer on the surface of Zn(OH)2 template. The abundant hydroxyl groups on Zn(OH)2 afford strong coordination ability with cations and help to the coating of a shell layer. The rudimental Zn(OH)2 core is eliminated with ammonia solution. In addition, ZnO-based heterostructures possessing better chemical or physical properties can also be prepared via this unique templating process. Room-temperature photoluminescence spectra of the heterostructures and hollow structures are also shown to study their optical properties

Wavelet penalized likelihood estimation in generalized functional models

The paper deals with generalized functional regression. The aim is to estimate the influence of covariates on observations, drawn from an exponential distribution. The link considered has a semiparametric expression: if we are interested in a functional influence of some covariates, we authorize others to be modeled linearly. We thus consider a generalized partially linear regression model with unknown regression coefficients and an unknown nonparametric function. We present a maximum penalized likelihood procedure to estimate the components of the model introducing penalty based wavelet estimators. Asymptotic rates of the estimates of both the parametric and the nonparametric part of the model are given and quasi-minimax optimality is obtained under usual conditions in literature. We establish in particular that the LASSO penalty leads to an adaptive estimation with respect to the regularity of the estimated function. An algorithm based on backfitting and Fisher-scoring is also proposed for implementation. Simulations are used to illustrate the finite sample behaviour, including a comparison with kernel and splines based methods