ABSTRACT
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 CD49f(high) cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49f(low) 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 CD49f(high) cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49f(high) 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.
Subject(s)
Biomarkers, Tumor/metabolism , Integrin alpha6/metabolism , Neoplastic Stem Cells/metabolism , Spheroids, Cellular/metabolism , Stomach Neoplasms/metabolism , Animals , Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Floxuridine/pharmacology , Fluorouracil/pharmacology , Humans , Inhibitory Concentration 50 , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Neoplasm Transplantation , Stomach Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Adult , Age Factors , Depressive Disorder, Major/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Remission Induction , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND: Past neuropsychological studies on depression have documented executive dysfunction and it has been reported that some dysfunction persists even after depressive symptoms disappear. Studies have shown a correlation between cerebrovascular lesions and executive dysfunction in depression among the elderly. The aim of the present study was to focus on executive functions in remitted major depressive disorder (MDD) patients, and to investigate whether remitted young and elderly patients show different patterns of executive dysfunction, and to ascertain the relationships with vascular lesions. METHODS: Subjects were 79 inpatients with MDD and 85 healthy controls. Each subject received Wisconsin Card Sorting Test (WCST), Stroop test, and Verbal Fluency Test (VFT) in a remitted state. Both the MDD and control groups were divided into young and elderly groups, and the performances between 4 groups were compared. RESULTS: For Stroop test, the scores of the MDD group were significantly lower than controls. In addition, as for VFT, the scores for the elderly MDD group were significantly lower than the other groups. Multiple regression analysis showed that VFT scores were affected by the presence of vascular lesions. CONCLUSIONS: The results of the present study demonstrated that executive dysfunction remained even in a remitted state in MDD patients, but the patterns of impairment were different between young and elderly patients. The results also suggested that vascular lesions affect executive dysfunction, particularly in elderly depressive patients.
