Hypothyroidism Enhances Tumor Invasiveness and Metastasis Development

11 pages, 9 figures.[Background]: Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients [Methodology/Principal Findings]: In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRβ1–expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRβ–expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs. [Conclusions/Significance]: These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.This work was supported by grants BFU2007-62402 from MEC; RD06/0020/0036 from FIS and from the EU Project CRESCENDO (FP6-018652.Peer reviewe

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (P<0.0001) as well as invasion depth (P<0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK

The petrogenesis of sodic island arc magmas at Savo volcano, Solomon Islands

Savo, Solomon Islands, is a historically active volcano dominated by sodic, alkaline lavas, and pyroclastic rocks with up to 7.5 wt% Na2O, and high Sr, arc-like trace element chemistry. The suite is dominated by mugearites (plagioclase–clinopyroxene–magnetite ± amphibole ± olivine) and trachytes (plagioclase–amphibole–magnetite ± biotite). The presence of hydrous minerals (amphibole, biotite) indicates relatively wet magmas. In such melts, plagioclase is relatively unstable relative to iron oxides and ferromagnesian silicates; it is the latter minerals (particularly hornblende) that dominate cumulate nodules at Savo and drive the chemical differentiation of the suite, with a limited role for plagioclase. This is potentially occurring in a crustal “hot zone”, with major chemical differentiation occurring at depth. Batches of magma ascend periodically, where they are subject to decompression, water saturation and further cooling, resulting in closed-system crystallisation of plagioclase, and ultimately the production of sodic, crystal and feldspar-rich, high-Sr rocks. The sodic and hydrous nature of the parental magmas is interpreted to be the result of partial melting of metasomatised mantle, but radiogenic isotope data (Pb, Sr, Nd) cannot uniquely identify the source of the metasomatic agent. Electronic supplementary material The online version of this article (doi:10.1007/s00410-009-0410-9) contains supplementary material, which is available to authorized users

Tsunami simulations on several scales - Comparison of approaches with unstructured meshes and nested grids

The tsunami event generated by the great Sumatra-Andaman earthquake on 26 December 2004 was simulated with the recently developed model TsunAWI. The model is based on the finite element method, which allows for a very flexible discretization of the model domain. This is demonstrated by a triangulation of the whole Indian Ocean with a resolution of about 14 km in the deep ocean but a considerably higher resolution of about 500 m in the coastal area. A special focus is put on the Banda Aceh region in the Northern tip of Sumatra. This area was heavily hit by the tsunami and the highest resolution in this area is about 40 m in order to include inundation processes in the model simulation. We compare model results to tide gauge data from all around the Indian Ocean, to satellite altimetry, and field measurements of flow depth in selected locations of the Aceh region. Furthermore, we compare the model results of TsunAWI to the results of a nested grid model (TUNAMI-N3) with the same initial conditions and identical bathymetry and topography in the Aceh region. It turns out that TsunAWI gives accurate estimates of arrival times in distant locations and in the same mesh gives good inundation results when compared to field measurements and nested grid results