No abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractLung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer-related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF-elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients. K E Y W O R D S CD109, EGFR, lung cancer, metastasis, mTOR | 1653 LEE Et aL.

Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α(-/-)) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP(+)GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP(+)GSCs. The hypoxic-AP(+)GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP(+)GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP(+)GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP(+)GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide due to its generally poor prognosis. Caregiver burden for liver cancer cases is higher than with other cancer and needs especial attention. Methods: To explore the experiences of families of patients with newly diagnosed advanced terminal stage hepatocellular cancer by interview. Results: Nine participants were recruited in this study. Content analysis of the interviews revealed four themes: blaming oneself, disrupting the pace of life, searching all possible regimens, and not letting go. Conclusions: This study provides new insight into the needs and support of family members especially when they are facing loved ones with newly diagnosed advanced terminal stage HCC. These results will inform future supportive care service development and intervention research aimed at providing assistance in reducing unmet supportive care needs and psychological distress of these family members.

Sleep, a basic physiological need of all humans, appears to be both integrative and restorative. However, studies have reported that 33-51% of women show a dramatic increase in sleep disturbance in the mid-life years, a time when they enter menopause. The purposes of this study were to (1) explore the prevalence of poor sleep quality in menopausal women; (2) identify the relationship between sleep quality of menopausal women and its related factors; (3) predict the possible explanations of how the related variables affect sleep quality of menopausal women; and (4) provide recommendations for future strategies that aim to improve sleep quality of menopausal women. A cross-sectional, correlation coefficient design was used. Purposive sampling was employed to recruit 197 menopause women from a small town in central Taiwan. T-test, one-way ANOVA, and multiple regression were used for data analysis. The results were as follows: (1) overall, the total score for sleep quality was 5.55 ± 3.47; 57.9% of subjects were identified as good sleepers and 42.1% as poor sleepers; (2) there were significant differences in quality of sleep related to occupational situation, history of chronic disease, menopausal status, number of chronic diseases, and number of menopausal symptoms (t = -3.49, -3.37, p < .01; F = 3.62, p < .05, F = 4.95, 5.35, p < .01); (3) depression and aging were strongly related to quality of sleep (r = .57; .22, p < .01); (4) 36% of variance in quality of sleep can be explained by depression and aging.