Triple-negative breast cancer (TNBC) exhibits more traits possessed by cancer stem cells (CSC) than other breast cancer subtypes and is more likely to develop brain metastases. TNBC patients usually have shorter survival time after diagnosis of brain metastasis, suggesting an innate ability of TNBC tumor cells in adapting to the brain. In this study, we establish novel animal models to investigate early tumor adaptation in brain metastases by introducing both patient-derived and cell line-derived CSC-enriched brain metastasis tumorsphere cells into mice. We discovered astrocyte-involved tumor activation of protocadherin 7 (PCDH7)-PLCβ-Ca2+-CaMKII/S100A4 signaling as a mediator of brain metastatic tumor outgrowth. We further identified and evaluated the efficacy of a known drug, the selective PLC inhibitor edelfosine, in suppressing the PCDH7 signaling pathway to prohibit brain metastases in the animal models. The results of this study reveal a novel signaling pathway for brain metastases in TNBC and indicate a promising strategy of metastatic breast cancer prevention and treatment by targeting organ-adaptive cancer stem cells. These findings identify a compound to block adaptive signaling between cancer stem cells and brain astrocytes. .

Introduction: China has been severely affected by coronavirus disease 2019 (COVID-19) since December 2019. Military healthcare workers in China have experienced many pressures when combating COVID-19. This study aimed to investigate the current psychological status and associated risk factors among military healthcare workers.Methods: We collected data from 194 military healthcare workers from three inpatient wards in two specialized COVID-19 hospitals using a web-based cross-sectional survey. The survey covered demographic information, the patient health questionnaire-9, the Generalized Anxiety Disorder-7, and the patient health questionnaire-15. Hierarchical regression analysis was used to explore potential risk factors for mental health problems.Results: The overall prevalence rates of depressive, generalized anxiety, and somatic symptoms were 37.6%, 32.5%, and 50%, respectively. Rates of severe depression, generalized anxiety, and somatic symptoms were 5.2%, 3.6%, and 15.5%, respectively. In 22.7% of cases, comorbidities existed between depression, generalized anxiety, and somatization. A junior-grade professional title was associated with depression, older age was associated with generalized anxiety and somatization, and short sleep duration and poor sleep quality were associated with all three symptoms.

Convincing epidemiological data suggest an inverse association between cancer and neurodegeneration, including Alzheimer's disease (AD). Since both AD and cancer are characterized by abnormal, but opposing cellular behavior, i.e., increased cell death in AD while excessive cell growth occurs in cancer, this motivates us to initiate the study into unraveling the shared genes and cell signaling pathways linking AD and glioblastoma multiform (GBM). In this study, a comprehensive bioinformatics analysis on clinical microarray datasets of 1,091 GBM and 524 AD cohorts was performed. Significant genes and pathways were identified from the bioinformatics analyses – in particular ERK/MAPK signaling, up-regulated in GBM and Angiopoietin Signaling pathway, reciprocally up-regulated in AD – connecting GBM and AD (P < 0.001), were investigated in details for their roles in GBM growth in an AD environment. Our results showed that suppression of GBM growth in an AD background was mediated by the ERK-AKT-p21-cell cycle pathway and anti-angiogenesis pathway.