Identification of gastric tumor-initiating cells (TICs) is essential to explore new therapies for gastric cancer patients. There are reports that gastric TICs can be identified using the cell surface marker CD44 and that they form floating spheres in culture, but we could not obtain consistent results with our patient-derived tumor xenograft (PDTX) cells. We thus searched for another marker for gastric TICs, and found that CD49fhigh cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49flow cells did not when subcutaneously injected into immunodeficient mice. These results indicate that CD49f, a subunit of laminin receptors, is a promising marker for human gastric TICs. We established a primary culture system for PDTX cells where only CD49fhigh cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49fhigh sphere cells formed tumors with histological features of parental ones, indicating that only TICs could grow in the culture system. Using this system, we found that some sphere-forming TICs were more resistant than gastric tumor cell lines to chemotherapeutic agents, including doxorubicin, 5-fluorouracil and doxifluridine. There was a patient-dependent difference in the tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs. These results suggest that ECM plays an essential role for the growth of TICs, and that this culture system will be useful to find new drugs targeting gastric TICs.
The authors aimed to investigate whether remitted adult and elderly major depressive disorder patients show different patterns of executive dysfunction. Executive functions of 20 euthymic major depressive disorder patients and 29 healthy comparison subjects were evaluated using the Behavioral Assessment of the Dysexecutive Syndrome. Relative to adult patients and healthy comparison subjects, euthymic elderly patients were more impaired in the subtest of Modified Six Elements. Since the regions most implicated in this subtest are the medial prefrontal, the anterior cingulate, and the dorsolateral prefrontal areas, the authors conclude that dysfunctions of such frontal neural networks remain unresolved even in the remission phase of late-life depression.
in 2009. Since nearly half of all new cases had suffered delirium, we subsequently launched our Delirium Control Team in 2011. The main purposes of the Delirium Control Team are to prevent the occurrence of delirium through early interventions by various medical staff, and to educate co-medical staff about delirium care. In this article, we present the recent activities and future outlook of both the Psychiatry Liaison Team and the Delirium Control Team.
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