RESUMO
Group climate in residential youth care is considered to be essential for treatment of youth and young adults. Various instruments exist to measure quality of living group climate, but some are lengthy, use complicated wording, which make them difficult to fill out by youth and individuals with a mild intellectual disability. The present study describes the development and rationale for the Group Climate Instrument-Revised (GCI-R). Construct validity and reliability of the GCI-R were examined by means of Confirmatory Factor Analysis (CFA) in a two-step validation process using a construction sample (n = 190 youth, representing 41 groups) and a validation sample (n = 207 youth, representing 42 groups). Results indicated a good fit of a five-factor model (Support, Growth, Physical Environment, Peer interactions, and Repression). Reliability of the scales was good. These findings indicate that the GCI-R can be used as a parsimonious, valid, and reliable instrument to assess perceptions of group climate in youth. Recommendations for future research and practice are suggested.
RESUMO
Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.