Nao Tanaka

Cognitive patterns and depression: Study of a Japanese university student population

Abstract  According to Beck’s cognitive theory, individuals who endure negative self‐schemas (dysfunctional attitudes) are more likely to present automatic thoughts consisting of negative schemata of oneself and one’s world while experiencing depression. In order to examine the relationships between depression, automatic thought, and dysfunctional attitude, 329 Japanese university students were given a set of questionnaires, including the Center for Epidemiologic Studies Depression Scale (CES‐D), Automatic Thought Questionnaire‐revised (ATQ‐R), and Dysfunctional Attitude Scale (DAS). A structural equation model revealed that depression was predicted predominantly by automatic thought, which was in turn predicted by dysfunctional attitude. The male gender had a tendency to predict dysfunctional attitude. The link between a student’s depression and dysfunctional attitude was mediated by automatic thought.

Correlates of the categories of adolescent attachment styles: Perceived rearing, family function, early life events, and personality

Aims:  To identify the psychosocial correlates of adolescents.

Involvement of Autophagy in Antitumor Activity of Folate-appended Methyl-β-cyclodextrin

Autophagy, the major lysosomal pathway for recycling intracellular components including organelles, is emerging as a key process regulating tumorigenesis and cancer therapy. Most recently, we newly synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD), and demonstrated the potential of FA-M-β-CyD as a new antitumor drug. In this study, we investigated whether anticancer activity of FA-M-β-CyD in folate receptor-α (FR-α)-positive tumor cells is involved in autophagy. In contrast to methyl-β-cyclodextrin (M-β-CyD), FA-M-β-CyD entered KB cells (FR-α (+)) through CLIC/GEEC endocytosis. No significant depression in the DNA content was observed in KB cells after treatment with FA-M-β-CyD. Additionally, the transmembrane potential of mitochondria after treatment with FA-M-β-CyD was drastically elevated. Meanwhile, FA-M-β-CyD induced the formation of autophagic vacuoles, which were partially colocalized with mitochondria, in KB cells. Taken together, these results suggest that FR-α-expressing cell-selective cytotoxic activity of FA-M-β-CyD could be mediated by the regulation of autophagy, rather than the induction of apoptosis.

Contribution of Perceived Rearing to Depression: The Role of Cognitive Patterns as a Mediator

To test possible mediation of the effects of the perceived parenting in childhood on depression, university stu- dents (N = 258) were examined using a cross-sectional questionnaire survey. A path model indicated that (1) the effects of dysfunctional attitude (rated by the Dysfunctional Attitude Scale) on depression (rated by the Center for Epidemiologic Studies Depression Scale) was mediated by automatic thoughts (rated by the Automatic Thought Questionnaire-Revised), (2) the effects of perceived rearing on depression were mediated by dysfunctional attitudes and automatic thoughts, and (3) perceived rearing was influenced by the gender of the student. These findings suggest that the well-studied link be- tween childhood experiences and adult depression are mediated by depression-related cognitive styles.

Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

Mitophagy is the specific autophagic elimination system of mitochondria, which regulates cellular survival via the removal of damaged mitochondria. Recently, we revealed that folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) provides selective antitumor activity in folate receptor-α (FR-α)-expressing cells by the induction of autophagy. In this study, to gain insight into the detailed mechanism of this antitumor activity, we focused on the induction of mitophagy by the treatment of FR-α-expressing tumor cells with FA-M-β-CyD. In contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered KB cells, human epithelial cells from a fatal cervical carcinoma (FR-α (+)) through FR-α-mediated endocytosis. The transmembrane potential of isolated mitochondria after treatment with FA-M-β-CyD was significantly elevated. In addition, FA-M-β-CyD lowered adenosine triphosphate (ATP) production and promoted reactive oxygen species production in KB cells (FR-α (+)). Importantly, FA-M-β-CyD enhanced light chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-α (+)) and induced PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in the induction of mitophagy. Furthermore, FA-M-β-CyD had potent antitumor activity in BALB/c nu/nu mice xenografted with KB cells (FR-α (+)) without any significant side effects. Taken together, these findings demonstrate that the autophagic cell death elicited by FA-M-β-CyD could be associated with mitophagy induced by an impaired mitochondrial function.

Evaluation of Antitumor Effects of Folate-Conjugated Methyl-β-cyclodextrin in Melanoma

Melanoma is a life-threatening disorder and its incidence is increasing gradually. Despite the numerous treatment approaches, conventional systemic chemotherapy has not reduced the mortality rate among melanoma patients, probably due to the induction of toxicity to normal tissues. Recently, we have developed folate-conjugated methyl-β-cyclodextrin (FA-M-β-CyD) and clarified its potential as a new antitumor agent involved in autophagic cell death. However, it remains uncertain whether FA-M-β-CyD exerts anticancer effects against melanomas. Therefore, in this study, we investigated the effects of FA-M-β-CyD on the folate receptor-α (FR-α)-expressing melanoma cell-selective cytotoxic effect. FA-M-β-CyD showed cytotoxic effects in Ihara cells, a human melanoma cell line expressing FR-α. In sharp contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered Ihara cells [FR-α(+)] through FR-α-mediated endocytosis. Additionally, FA-M-β-CyD elicited the formation of autophagosomes in Ihara cells. Notably, FA-M-β-CyD suppressed melanoma growth in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double deficient mice bearing Ihara cells. Therefore, these results suggest that FA-M-β-CyD could be utilized as a potent anticancer agent for melanoma chemotherapy by regulating autophagy.