Metastasis is a major obstacle that must be overcome for the successful treatment of lung cancer. Proteins secreted by cancer cells may facilitate the progression of metastasis, particularly within the phases of migration and invasion. To discover metastasis-promoting secretory proteins within cancer cells, we used the label-free quantitative proteomics approach and compared the secretomes from the lung adenocarcinoma cell lines CL1-0 and CL1-5, which exhibit low and high metastatic properties, respectively. By employing quantitative analyses, we identified 660 proteins, 68 of which were considered to be expressed at different levels between the two cell lines. Lung cancer is the leading cause of cancer death, and ϳ90% of all lung cancer deaths are attributed to metastases (1). Approximately 95% of lung cancer patients are not diagnosed until they develop symptoms, and 85% of the newly diagnosed lung cancer patients are already in the advanced stages of the disease (2, 3). Once the tumor cells have metastasized and spread throughout the lungs, the cancer is considerably more difficult to treat. Invasiveness and metastasis are major threats to successful treatment. Cancer metastasis is an intricate, multi-step process in which the tumor cells must gain both migratory and invasive properties (4). In metastasis research, there are two common in vivo models, spontaneous and experimental metastasis (5-7). In brief, spontaneous metastasis refers to primary tumor cells that are able to dissociate from the primary tumor and metastasize to the secondary organ via the circulatory system. In contrast, experimental metastasis refers to the injection of tumor cells directly into the systemic circulation. Many researchers have attempted to determine the molecular basis of these transitions in hopes of developing target-specific drugs or biomarkers for the prevention and diagnosis of metastasis. Although there have been many discoveries regarding a particular proFrom the ‡Department

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Integrating multifactor blood analysis is a key step toward a precise diagnosis of the health status of marine mammals. Variations in the circulating lipid profile reflect changes in the metabolism and physiology of an individual. To demonstrate the practicability of lipid profiling for physiological assessment, the phosphorylcholinecontaining lipids in the plasma of long-term managed beluga whales (Delphinapterus leucas) were profiled using a lipidomics methodology. Using a multivariate analysis, the mean corpuscular volume, cholesterol, potassium, and γ-glutamyltranspeptidase levels were well modeled with the lipid profile of the female whales. In the models, the correlated lipids provided information about blood parameter-related metabolism and physiological regulation, in particular relating to cholesterol and inflammation. In the males, the levels of cholesterol, triglycerides, blood urea nitrogen, creatinine, plasma iron, and segmented neutrophil were well modeled with the lipid profile. In addition to providing information about the related metabolism and regulation, through a crosslinked analysis of the blood parameters, the correlated lipids indicated a parallel regulation involved in the energy metabolism of the male whales. Lipidomics as a method for revealing the context of physiological change shows practical potential for the health care of managed whales. K E Y W O R D Sblood test, captive animal, phospholipid, plasma lipids, PPAR

Previous research has shown that left posterior middle temporal gyrus (pMTG) is a core node in the semantic network, and cross-sectional studies have shown that activation in this region changes developmentally and is related to skill measured concurrently. However, it is not known how functional connectivity with this region changes developmentally, and whether functional connectivity is related to future gains in reading. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study in 30 typically developing children (aged 8–15) to examine whether initial brain measures, including activation and connectivity, can predict future behavioral improvement in a semantic judgment task. Participants were scanned on entering the study (time 1) and a follow-up period of 2 years (time 2). Character pairs were arranged in a continuous variable according to association strength (i.e. strong versus weak), and participants were asked to determine if these visually presented pairs were related in meaning. Our results demonstrated greater developmental changes from time 1 to time 2 for weaker association pairs in the left pMTG for the children (aged 8–11) as compared to the adolescents (aged 12–15). Moreover, the results showed greater developmental changes from time 1 to time 2 for weaker association pairs in connectivity between the pMTG and inferior parietal lobule (IPL) for the children as compared to the adolescents. Furthermore, a hierarchical stepwise regression model revealed that connectivity between the pMTG and IPL in weak association pairs was uniquely predictive of behavioral improvement from time 1 to time 2 for the children, but not the adolescents. Taken together, the activation results suggest relatively rapid development before adolescence of semantic representations in the pMTG. Moreover, the connectivity results of pMTG with IPL tentatively suggest that early development of semantic representations may be facilitated by enhanced engagement of phonological short-term memory.