Search

Background: Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR) of hepatocellular carcinoma (HCC). Methods: A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential) and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs) treated with tanshinone IIA. Results: PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT) in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α) or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR) upregulation. Although the microvessel density (MVD) of residual tumor tissue increased after PR, the microvessel integrity (MVI) was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions: Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical benefit of preventing postsurgical recurrence. [ABSTRACT FROM AUTHOR]

Tidal-stream turbines spend most of time in a shear flow environment, which leads to non-uniformity effect in stream vertical profile. To better understanding of such effect on tidal-stream turbine performance, the hydrodynamic performance and comparison between a bare turbine and a diffuser-augmented turbine under shear flow condition were numerically investigated. To closer to the real working environment of tidal-stream turbine, three major factors influence on hydrodynamic performance including flow shear rates, yaw angle and arrangement rule in array were discussed in detail. It is found that the different shear rate of flow will result in power and axis thrust slightly amplitude comparing with the uniform flow, and a diffuser turbine will further amplify this effect comparing with a bare turbine. The greater the yaw angle is, the more power and axis thrust is reduced. Additionally, there are "Advantageous Interaction" and "Disadvantage Interaction" in the wake effect on the energy extraction performance in the turbine array. The output power for each case is relatively concentrated at lower tip speed ratio (TSR) and divergent at higher TSR. Furthermore, each turbine in array operating at near 2 D flow distance and relative deviation angle of 45° reaches its maximum C P. • Hydrodynamic performance comparison between a bare turbine and a diffuser turbine under shear flow. • Influence on hydrodynamic performance of flow shear rates, yaw angle and arrangement rule in array was discussed. • Each turbine in array at near 2 D flow distance and relative deviation angle of 45° reaches its maximum efficiency. [ABSTRACT FROM AUTHOR]

Purpose: Antibodies targeting GD3 gangliosides highly expressed on melanomas mediate immune effector functionsin vitro and inhibit animal model melanoma tumor growthin vivo. Because GD3 is expressed also on a subpopulation of human lymphocytes, we characterized thein vitro immune effects of murine R24 and a chimeric anti-GD3 antibody (KW-2871). Design: Anti-GD3 complement-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested against cell line Mel-624. Antibody-mediated lymphocyte expression of interleukin (IL)-2, IL-4, IL-10, and interferon-γ (IFN-γ) was quantified. The effect of antibody and antibody-treated lymphocyte supernates on effector cell ADCC and Fc receptor expression were evaluated. Results: R24 and KW-2871 antibodies mediated CMC and ADCC to the Mel-624 cell line. R24 induced potent lymphocyte proliferation and enhanced lymphocyte RNA expression of IL-4 (2–4 logs), IL-10, and IFN-γ (> 10-fold). KW-2871 induced no lymphocyte proliferation and had minimal effects on lymphokine expression (< 5-fold). Preincubation of effector cells with either antibody inhibited ADCC and reduced monocyte expression of FcγRI and II. Supernates of effector cells preincubated with either antibody were able to inhibit ADCC. Conclusions: R24 and KW-2871 antibody differ in their lymphocyte proliferation and lymphokine release activity but have similar inhibition of lymphocyte ADCC and FcγR expressionin vitro. [ABSTRACT FROM AUTHOR]

The phases and magnetic properties of Co-Zr-C melt-spun ribbon were studied. The Co80Zr20 melt-spun ribbon consisted of a metastable Co5Zr phase together with fcc-Co and Co23Zr6 phases and showed a high coercivity. The small substitution of C for Zr in the Co-Zr melt-spun ribbon resulted in the increase in the saturation magnetization. However, the substitution resulted in the decrease in the coercivity. Unlike the Co-Zr melt-spun ribbon, annealing of the Co-Zr-C melt-spun ribbon resulted in the further decrease in the coercivity. Thermomagnetic studies showed that the Co-Zr-C melt-spun ribbon consisted of the new magnetic phase with a high Curie temperature and a high-saturation magnetization. X-ray diffraaction studies of the Co-Zr-C melt-spun ribbon revealed that the new magnetic phase with a high Curie temperature and a high-saturation magnetization is believed to be the Co11Zr2 phase. [ABSTRACT FROM AUTHOR]

Background: microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages. Methods: Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC. Results: Ectopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC. Conclusions: miR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC. [ABSTRACT FROM AUTHOR]

Background: The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Methods: Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. Results: MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelialmesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). Conclusions: The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC. [ABSTRACT FROM AUTHOR]

Purpose: KW-2871 (IgG1 kappa chimeric antibody) targets GD3, which is upregulated in melanomas. We conducted a phase I trial of KW-2871 in patients with metastatic melanoma. Methods: Seventeen (17) patients were enrolled and received an initial test dose (10 mg/m2) intravenously. Two (2) weeks later, patients were stratified into 4 cohorts to receive 4 doses of KW-2871 (infused over 1 hour) at 2-week intervals (20, 40, 60, and 80 mg/m2). No premedications were administered for the test or first therapeutic doses. Results: Dose-limiting toxicities were Grade 3 laryngospasm and chest tightness with the initial therapeutic infusion at doses of 80 and 60 mg/m2. The maximum tolerated dose (MTD) was established at 40 mg/m2of KW2871. The most common side-effect was urticaria (Grades 1–3) in 16 of 16 patients during an initial therapeutic infusion without premedication. The mean terminal half-life, clearance, and area under the concentration-time curve (AUC0-t) at a dose of 40 mg/m2for course 1 were 146 ± 31 hours, 28 ± 6 ml/hour, and 1922 ± 491 mcg*hour/mL, respectively. Anti-human chimeric antibody was not detected. Two (2) patients in the 40 mg/m2cohort had stable disease. Conclusions: An MTD of 40 mg/m2without premedication was established for KW-2871, with urticaria being the most common sideeffect and dose-limiting anaphylactoid infusion reactions. [ABSTRACT FROM AUTHOR]

The tensile strength and ductility of a high nitrogen nickel-free austenitic stainless steel with solution and cold rolling treatment were investigated by performing tensile tests at different strain rates and at room temperature. The tensile tests demonstrated that this steel exhibits a significant strain rate and cold rolling dependence of the tensile strength and ductility. With the increase of the strain rate from 10−4 s−1 to 1 s−1, the yield strength and ultimate tensile strength increase and the uniform elongation and total elongation decrease. The analysis of the double logarithmic stress—strain curves showed that this steel exhibits a two-stage strain hardening behavior, which can be well examined and analyzed by using the Ludwigson equation. The strain hardening exponents at low and high strain regions (n2 and n1) and the transition strain (εL) decrease with increasing strain rate and the increase of cold rolling RA. Based on the analysis results of the stress–strain curves, the transmission electron microscopy characterization of the microstructure and the scanning electron microscopy observation of the deformation surfaces, the significant strain rate and cold rolling dependence of the strength and ductility of this steel were discussed and connected with the variation in the work hardening and dislocation activity with strain rate and cold rolling. [ABSTRACT FROM AUTHOR]