5 research outputs found

    Subduction controls of Hf and Nd isotopes in lavas of the Aleutian island arc

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    The Hf and Nd isotopic compositions of 71 Quaternary lavas collected from locations along the full length of the Aleutian island arc are used to constrain the sources of Aleutian magmas and to provide insight into the geochemical behavior of Nd and Hf and related elements in the Aleutian subduction-magmatic system. Isotopic compositions of Aleutian lavas fall approximately at the center of, and form a trend parallel to, the terrestrial Hf-Nd isotopic array with {var_epsilon}{sub Hf} of +12.0 to +15.5 and {var_epsilon}{sub Nd} of +6.5 to +10.5. Basalts, andesites, and dacites within volcanic centers or in nearby volcanoes generally all have similar isotopic compositions, indicating that there is little measurable effect of crustal or other lithospheric assimilation within the volcanic plumbing systems of Aleutian volcanoes. Hafnium isotopic compositions have a clear pattern of along-arc increase that is continuous from the eastern-most locations near Cold Bay to Piip Seamount in the western-most part of the arc. This pattern is interpreted to reflect a westward decrease in the subducted sediment component present in Aleutian lavas, reflecting progressively lower rates of subduction westward as well as decreasing availability of trench sediment. Binary bulk mixing models (sediment + peridotite) demonstrate that 1-2% of the Hf in Aleutian lavas is derived from subducted sediment, indicating that Hf is mobilized out of the subducted sediment with an efficiency that is similar to that of Sr, Pb and Nd. Low published solubility for Hf and Nd in aqueous subduction fluids lead us to conclude that these elements are mobilized out of the subducted component and transferred to the mantle wedge as bulk sediment or as a silicate melt. Neodymium isotopes also generally increase from east to west, but the pattern is absent in the eastern third of the arc, where the sediment flux is high and increases from east to west, due to the presence of abundant terrigenous sediment in the trench east of the Amlia Fracture Zone, which is being subducting beneath the arc at Seguam Island. Mixing trends between mantle wedge and sediment end members become flatter in Hf-Nd isotope space at locations further west along the arc, indicating that the sediment end member in the west has either higher Nd/Hf or is more radiogenic in Hf compared to Nd. This pattern is interpreted to reflect an increase in pelagic clay relative to the terrigenous subducted sedimentary component westward along the arc. Results of this study imply that Hf does not behave as a conservative element in the Aleutian subduction system, as has been proposed for some other arcs

    Intravenous administration of adenoviruses targeting transforming growth factor beta signaling inhibits established bone metastases in 4T1 mouse mammary tumor model in an immunocompetent syngeneic host

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    We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFβRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTβRFc, or with two oncolytic adenoviruses, Ad.sTβRFc and TAd.sTβRFc, expressing sTGFβRIIFc (the human TERT promoter drives viral replication in TAd.sTβRFc) produced sTGFβRIIFc protein. Oncolytic adenoviruses produced viral replication and induced cytotoxicity in 4T1 cells. 4T1 cells were resistant to the cytotoxic effects of TGFβ-1 (up to 10 ng/ml). However, TGFβ-1 induced the phosphorylation of SMAD2 and SMAD3, which were inhibited by co-incubation with sTGFβRIIFc protein. TGFβ-1 also induced IL-11, a well-known osteolytic factor. Intracardiac injection of 4T1-luc2 cells produced bone metastases by day 4. Intravenous injection of Ad.sTβRFc (on days 5 and 7) followed by bioluminescence imaging (BLI) of mice on days 7, 11 and 14 in tumor bearing mice indicated inhibition of bone metastasis progression (p<0.05). X-ray radiography of mice on day 14 showed a significant reduction of the lesion size by Ad.sTβRFc (p<0.01) and TAd.sTβRFc (p<0.05). Replication-deficient virus Ad(E1-).sTβRFc expressing sTGFβRIIFc showed some inhibition of bone metastasis, while Ad(E1-).Null was not effective in inhibiting bone metastases. Thus, systemic administration of Ad.sTβRFc and TAd.sTβRFc can inhibit bone metastasis in the 4T1 mouse mammary tumor model, and can be developed as potential anti-tumor agents for breast cancer
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