MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

Background\ud The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer.\ud \ud Methods\ud The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo.\ud \ud Results\ud MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo.\ud \ud Conclusions\ud This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer

The last three millions of unequal spring thaws

Evidence from various climate proxies provides us with increasingly reliable proof that only in the past 10 millennia were natural systems more or less as we see them at the present (without considering human impact). Prior to 10,000 years ago, natural systems repeatedly changed under the influence of an unstable climate. This is particularly true over the last one million years. During these times, terrestrial environments were populated by a diversity of large animals that did not survive either the last dramatic climate change or the increasing power of humans. The volume of continental ice covering the land and its impact on the planet’s physiography∗ and vegetation have varied consistently. We can try to imagine extreme conditions: the very cold springtimes of the full glacials∗, and the warm springtimes of the rapid deglaciation phases, with enormous volumes of water feeding terrifying rivers. Most of this story is frozen in the ice cover of Greenland and Antarctica, the deep layers of which have been reached by human coring activities only over the past half century. Shorter cores have been drilled in high-altitude ice caps (e.g., in the Andes) that provide insight into other parts of the planet. The interpretation of the signals locked into the ice cores led to the reconstruction of climatic curves covering approximately the past 800 millennia. In addition, long sediment cores have been recovered from thousands of lakes across the globe and yielded data useful to estimate climatic trends based on pollen* records. In the past one to three million years, the continents and oceans were in roughly their present-day locations. Environmental factors, including tectonics (mountain uplift or closure of ocean gateways), interacted with the overall long-term oscillation in atmospheric carbon-dioxide concentration, which, in turn, influenced vegetation cover and ecosystem composition. Well-established glacial-interglacial∗ cycles impacted biotic dispersal∗ events at mid-to-high latitudes and determined the geographical restriction and expansion of tropical and subtropical (warm-temperate) biomes around the globe. This book chapter constitutes an imaginary field trip, presenting the reader with exemplary records of environments, plants, large mammals, and hominins impacted by cooling and warming phases, glaciations, changes in rainfall patterns, and sea level culminating in the world of today