Dislocation nucleation in shocked fcc solids: effects of temperature and preexisting voids

Quantitative behaviors of shock-induced dislocation nucleation are investigated by means of molecular dynamics simulations on fcc Lennard-Jones solids: a model Argon. In perfect crystals, it is found that Hugoniot elastic limit (HEL) is a linearly decreasing function of temperature: from near-zero to melting temperatures. In a defective crystal with a void, dislocations are found to nucleate on the void surface. Also HEL drastically decreases to 15 percent of the perfect crystal when a void radius is 3.4 nanometer. The decrease of HEL becomes larger as the void radius increases, but HEL becomes insensitive to temperature.Comment: 4 pages. (ver.2) All figures have been revised. Two citations are newly added. Numerical unit is unified in the context of solid argon. (ver. 3) A minor revision including new reference

Effect of psoralens and ultraviolet radiation on murine dendritic epidermal cells

AbstractMonofunctional psoralens produce less phototoxicity than bifunctional psoralens after ultraviolet A (UVA) irradiation. We investigated the effect of repetitive treatments with angelicin (isopsoralen), a monofunctional psoralen, plus UVA radiation (IPUVA) on the number and morphology of dendritic epidermal cells (dEC). This effect was compared with that of 8-methoxypsoralen plus UVA radiation (PUVA), UVA alone, and UVB radiation. C3H/HeN mice were treated topically with the drugs three times/wk for 4 consecutive wk; followed each time by 1 or 2.5 J/cm2 of UVA radiation. Other groups of mice were treated with the drugs alone, UVA alone, or 0.81 J/cm2 of UVB. Epidermal sheets were stained for ATPase, Ia, and Thy-1 markers. Mice treated with PUVA and UVB exhibited severe phototoxicity, whereas no overt phototoxicity was observed in mice treated with IPUVA, UVA alone, or the drugs alone. Early during the PUVA and UVA treatments the ATPase marker was lost from dEC, followed by loss of the Ia marker; the Ia marker was lost before the ATPase marker from dEC in animals treated with IPUVA. At the end of the treatment, however, nearly total depletion of ATPase+, Ia+, and Thy-1+ dEC was observed in mice treated with PUVA and IPUVA. UVB radiation caused rapid depletion of Thy-1+ dEC as well as ATPase+ and Ia+ cells. During treatments with IPUVA, PUVA, UVA, and UVB, the Langerhans cells became rounded and lost their dendrites. These changes were quantitated by image analysis. We conclude that alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that monofunctional and bifunctional psoralens plus low dose of UVA radiation may have different effects on dEC markers

Bovine Aorta Endothelial Cell Incubation with Interleukin 2: Morphological Changes Correlate with Enhanced Vascular Permeability

Interleukin 2 induced alterations in the morphology of bovine aortic endothelial cells in vitro. The changes observed in confluent cultures of bovine aortic endothelial cells included retraction and elongation of eel ls leading to enlarged gaps between cells quantified by image analysis. Purified IL-2 (1 U/ml medium) increased the gaps between endothelial cells 3-4-fold compared with control cultures. The effect was transient, since the cells reverted to their original morphology 6-12 hours after the removal of lL-2. Correlative scanning electron microscopy (SEM) studies using fresh bovine aorta showed a dose-dependent alteration of the endothelial surface by IL-2 characterized by rounding and elongation of endothelial cells and prominent perinuclear areas. Gaps between the endothelial cells were observed when aorta samples were incubated with 2 U of IL-2/ml of medium. This was confirmed by SEM, transmission electron microscopy and Evans blue dye staining. These results suggest that IL-2 caused morphological alterations in endothelial cells that enhanced the permeability of the vascular endothelium

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA\u27s mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects

EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 μM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day−1mouse−1starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. © 2001 Cancer Research Campaign http://www.bjcancer.co

Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors

Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Antivascular therapy of human follicular thyroid cancer experimental bone metastasis by blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor phosphorylation

Patients suffering from bone metastases of Follicular Thyroid Carcinoma (FTC) have a poor prognosis because of the lack of effective treatment strategies. The overexpression of Epidermal Growth Factor Receptor (EGFR) associated with increased vascularity has been implicated in the pathogenesis of FTC and subsequent bone metastases. We hypothesized that inhibiting the phosphorylation of the EGFR and Vascular Endothelial Growth Factor Receptor (VEGFR) by AEE788, a dual tyrosine kinase inhibitor of EGFR and VEGFR, in combination with paclitaxel would inhibit experimental FTC bone lesions and preserve bone structure. We tested this hypothesis using the human WRO FTC cell line. In culture, AEE788 inhibited the EGF-mediated phosphorylation of EGFR, VEGFR2, mitogen-activated protein kinase and Akt in culture. AEE788, alone and in combination with paclitaxel, inhibited cell growth and induced apoptosis. When WRO cells were injected into the tibia of nude mice, tumor and endothelial cells within the lesions expressed phosphorylated EGFR, VEGFR, Akt and mitogen-activated protein kinase that were inhibited by the oral administration of AEE788. Therapy consisting of orally given AEE788 and i.p. injected paclitaxel induced a high level of apoptosis in tumor-associated endothelial cells and tumor cells with the inhibition of tumor growth in the bone and the preservation of bone structure. Collectively, these data show that blocking the phosphorylation of EGFR and VEGFR with AEE788 combined with paclitaxel can significantly inhibit experimental human FTC in the bone of nude mice