ABSTRACT
BST-2 is a novel driver of cancer progression whose expression confers oncogenic properties to breast cancer cells. As such, targeting BST-2 in tumors may be an effective therapeutic approach against breast cancer. Here, we sought to develop potent cytotoxic anti-cancer agent using the second-generation BST-2-based anti-adhesion peptide, B18, as backbone. To this end, we designed a series of five B18-derived peptidomimetics. Among these, B18L, a cationic amphiphilic α-helical peptidomimetic, was selected as the drug lead because it displayed superior anti-cancer activity against both drug-resistant and drug-sensitive cancer cells, with minimal toxicity on normal cells. Probing mechanism of action using molecular dynamics simulations, biochemical and membrane biophysics studies, we observed that B18L binds BST-2 and possesses membranolytic characteristics. Furthermore, molecular biology studies show that B18L dysregulates cancer signaling pathways resulting in decreased Src and Erk1/2 phosphorylation, increased expression of pro-apoptotic Bcl2 proteins, caspase 3 cleavage products, as well as processing of the caspase substrate, poly (ADP-ribose) polymerase-1 (PARP-1), to the characteristic apoptotic fragment. These data indicate that through the coordinated regulation of membrane, mitochondrial and signaling events, B18L executes cancer cell death and thus has the potential to be developed into a potent and selective anti-cancer compound.
ABSTRACT
The purpose of the current study was to make a case for instituting parent-child relational problem (PCRP) screening as a standard of care in pediatric inpatient psychiatric units due to increasing evidence that PCRP may be an underreported problem that affects more adolescents than currently realized. Adolescents who are admitted to the hospital for mood exacerbation, suicidal ideation, self-harm behavior, or behavioral escalation may improve and be discharged. However, these adolescents often are readmitted, which may be associated with parent-child relational factors. By identifying adolescents with PCRP and initiating holistic therapy/intervention that addresses the underlying cause of their PCRP, it may be possible to improve the parent-adolescent relationship and break the cycle of admission, discharge, and readmission. PCRP is increasingly recognized as a risk factor for development and progression of childhood mental illnesses. Investment in screening and treatment for PCRP may result in significant cost savings from prevention or reduction of rehospitalization and/or amelioration of disability. [Journal of Psychosocial Nursing and Mental Health Services, 56(9), 27-32.].
Subject(s)
Mood Disorders , Parent-Child Relations , Referral and Consultation , Surveys and Questionnaires , Adolescent , Female , Hospitalization , Humans , Male , Mental Health Services/organization & administration , Mood Disorders/diagnosis , Mood Disorders/therapy , Patient Discharge , Psychiatric Department, Hospital/statistics & numerical data , Risk Factors , Self-Injurious Behavior/psychologyABSTRACT
Parent-child relational problems (PCRP) have been increasingly recognized as a risk factor in the development and/or progression of childhood mental illnesses. Despite many young individuals being at risk, health care providers do not specifically screen for PCRP in children diagnosed with mental illnesses. The objective of the current project was to implement a PCRP screening program in a metropolitan children's hospital and refer those with PCRP for treatment. Adolescents ages 10 to 17 presenting for admission in an inpatient pediatric psychiatric unit were screened with the PCRP semi-structured questionnaire and diagnostic criteria developed by the American Psychiatric Association's Relational Processes Workgroup. Eleven (73%) of 15 patients screened were found to have PCRP. Patients may be screened with a PCRP screening tool during biopsychosocial assessment without undue time burden on the provider. It is recommended that PCRP be added to electronic health records so providers can select PCRP in problem lists as well as formulate PCRP-sensitive care plans. [Journal of Psychosocial Nursing and Mental Health Services, 55(11), 23-29.].
