Effects of Familial Relationships on School Adjustment of Adolescents and Young Adults With Congenital Heart Disease.

BACKGROUND: As more than 85% of patients with congenital heart disease (CHD) have grown to adulthood through improvement in treatment and surgery, the difficulties they experience are expanding into areas related to daily life. Accordingly, adjustment to school in adolescents and young adults (AYAs) with CHD is of increasing interest and is influenced by familial factors. OBJECTIVE: This was a cross-sectional descriptive study to examine the effects of parental positive emotional expressiveness and sibling relationships on school adjustment of AYAs with CHD. METHODS: In this study, a self-reported questionnaire survey was used to collect the data. The participants were 104 AYAs with CHD aged 13 to 21 years who were attending school and had siblings. RESULTS: Maternal positive emotional expressiveness ( r = 0.584, P < .01), paternal positive emotional expressiveness ( r = 0.584, P < .01), and sibling warmth/closeness ( r = 0.478, P < .01) were significantly correlated with school adjustment. However, the results of multiple regression analysis showed that only maternal positive emotional expressiveness (ß = 0.459, P < .05) and sibling warmth/closeness (ß = 0.236, P < .05) were significantly associated with school adjustment. CONCLUSIONS: Adolescents and young adults with CHD who reported higher maternal positive emotional expressiveness and sibling warmth/closeness exhibited better school adjustment. Findings suggest that intervention programs to increase parental positive expressiveness and enhance warmth/closeness of sibling relationships may contribute to improving school adjustment.

Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.

Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.

Comparison of perceived parental empathy between adolescents with leukemia and healthy adolescents: A comparative descriptive study.

Purpose: The purpose of this study was to investigate and compare perceived parental empathy between adolescents with and without leukemia. Methods: This study used a cross-sectional, descriptive design. Thirty-eight adolescents with leukemia and 205 without, completed a self-reported questionnaire regarding their perceptions of parental empathy and general characteristics. For this comparative study, adolescents were selected through matched sampling, and 38 adolescents per group were used for analysis. Data were examined using independent t-tests. Results: In terms of parental empathy, excessive emotional reactions and cold emotional reactions were perceived more frequently by adolescents with leukemia than healthy adolescents. Differences between the two groups were statistically significant. Conclusion: Since parents caring for children with leukemia have an extra burden in caring for their children, these parents are continuously anxious about prognoses, and tend to feel guilty for their child's disease. Thus, healthcare providers need to develop a program for improving the ability of parents of cancer patients to demonstrate empathy, focusing on how to recognize and manage what may be perceived by their children as excessive or cold emotional reactions, and must take a role in communicating to parents how adolescents with leukemia perceive parental rearing behaviors and the impacts of these behaviors on their well-being.

Sibling Relationships of Adolescents with Congenital Heart Disease.

Adolescents with congenital heart disease (CHD) continuously need family support because of their repeated follow ups, treatments, and complications. However, sibling relationships have not been well studied among adolescents with CHD. The purpose of the present study was to explore the relationships between adolescents with CHD and their siblings, and to examine these relationships according to birth order and age. Adolescents aged from 13 to 21 years who had been diagnosed with CHD and had siblings were included as participants. The Sibling Relationship Questionnaire (SRQ) was used. The SRQ consists of four factors: warmth/closeness, conflict, relative power/status, and rivalry. A univariate general linear model was conducted to identify the sibling relationship factors according to birth order and sibling ages. The score for relative power/status of participants who were the eldest sibling was higher than that of younger siblings. The score for rivalry increased as sibling age increased. Therefore, healthcare providers need to investigate sibling relationships and to explain the importance of self-identity and power balance between adolescents with CHD and their siblings to parents.

Identification of Thieno[3,2-d]pyrimidine Derivatives as Dual Inhibitors of Focal Adhesion Kinase and FMS-like Tyrosine Kinase 3.

Focal adhesion kinase (FAK) is overexpressed in highly invasive and metastatic cancers. To identify novel FAK inhibitors, we designed and synthesized various thieno[3,2-d]pyrimidine derivatives. An intensive structure-activity relationship (SAR) study led to the identification of 26 as a lead. Moreover, 26, a multitargeted kinase inhibitor, possesses excellent potencies against FLT3 mutants as well as FAK. Gratifyingly, 26 remarkably inhibits recalcitrant FLT3 mutants, including F691L, that cause drug resistance. Importantly, 26 is superior to PF-562271 in terms of apoptosis induction, anchorage-independent growth inhibition, and tumor burden reduction in the MDA-MB-231 xenograft mouse model. Also, 26 causes regression of tumor growth in the MV4-11 xenograft mouse model, indicating that it could be effective against acute myeloid leukemia (AML). Finally, in an orthotopic mouse model using MDA-MB-231, 26 remarkably prevents metastasis of orthotopic tumors to lymph nodes. Taken together, the results indicate that 26 possesses potential therapeutic value against highly invasive cancers and relapsed AML.

Ratio of Autoantibodies of Tumor Suppressor AIMP2 and Its Oncogenic Variant Is Associated with Clinical Outcome in Lung Cancer.

Aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) works as potent tumor suppressor, while its splicing variant lacking exon 2 (AIMP2-DX2) competes with AIMP2 for binding to target proteins and compromises its anti-tumor activity. Assuming that AIMP2 and its variant AIMP2-DX2 could be released out to human sera in pathological condition, we investigated the diagnostic and prognostic usefulness of autoantibodies against AIMP2 and AIMP2-DX2 by measuring their serum levels in 80 normal and lung cancer samples that were matched in age, gender and smoking status. The area under the curve of AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 autoantibody ratio was low (0.416, 0.579, and 0.357, respectively), suggesting limited diagnostic value. A total of 165 lung cancer patients were classified into low and high AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 based on the median expression of each parameter. The high AIMP2-DX2 group was older and had larger tumors (>3 cm) than the low AIMP2-DX2 group. The high AIMP2-DX2/AIMP2 group had higher CYFRA-21 levels and significantly shorter overall survival than the low AIMP2-DX2/AIMP2 group (18.6 vs. 48.9 months, P = 0.021, Log Rank Test). Taken together, autoantibodies against AIMP2-DX2 and AIMP2 are detectable in the human blood and the increased ratio of AIMP2-DX2/AIMP2 is related to poor clinical outcome of lung cancer.

Cyclic AMP suppresses matrix metalloproteinase-1 expression through inhibition of MAPK and GSK-3beta.

Expression of matrix metalloproteinase-1 (MMP-1) is stimulated by diverse stimuli and is likely to be regulated by many signaling pathways. cAMP is known to act as a second messenger for various extracellular stimuli and to be involved in the regulation of cell proliferation, apoptosis, and inflammation. Here, we investigated the effect of cAMP on tumor necrosis factor (TNF)-alpha-induced MMP-1 expression and the molecular events involved in the processes in human skin fibroblasts. We showed that cAMP suppresses TNF-alpha-induced MMP-1 expression via protein kinase A (PKA) pathway. cAMP inhibited TNF-alpha-stimulated ERK and JNK activation, which was shown to have an important role in MMP-1 expression. However, MMP-1 expression could also be inhibited by cAMP even when ERK and JNK activities were unaffected, indicating that there might be other target(s) that mediate cAMP-mediated suppression of MMP-1 expression. Further studies revealed that glycogen synthase kinase (GSK)-3beta can be inactivated by cAMP/PKA pathway and has important roles in MMP-1 expression, and showed that inactivation of GSK-3beta is critical for suppression of MMP-1 expression by cAMP elevation after TNF-alpha treatment. Taken together, our results suggest that cAMP/PKA pathway can suppress MMP-1 expression through inhibition of multiple signaling pathways, including MAPK and GSK-3beta.