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Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Most of the literature on countertransference reactions with criminals has emphasized negative emotions such as hatred, rage, and fear. This article discusses reactions that have been relatively neglected, such as fascination and envy. Fantasies of leading a life of excitement are frequently evoked. Recognizing these fantasies and emotions and accepting them as attractive can increase our understanding of the offender and his life. The lure of criminality, despite its severe consequences, becomes more understandable. Accepting these emotions can bring a challenge to life, and a reevaluation of one's morals and values. A balance between the reality of 'normal' life and fantasy is ultimately accepted.

The current study examines the differences between four groups of offenders (N = 230) according to the type of crime they committed: domestic violence, sex offenses, traffic violations, and nonspecific violence offenses. The study was conducted on the offenders undergoing treatment in the Israeli Adult Probation Service. A comparison between the groups included an examination of the differences in aggression levels, anxiety levels, and two Minnesota Multiphasic Personality Inventory–2 (MMPI-2) scales—the Psychopathic Deviate (PD-4) and the Antisocial Practices (ASP) scales. The findings provide a glimpse of the features that characterize each group, in relation to each other and in relation to the body of literature. The domestic violence group differed from the other groups in most of the research variables. They were found to have low anxiety levels and high aggression levels. Together with other findings that pointed to antisocial practices and attitudes, this group constitutes a population that is violent and aggressive to a far greater extent compared with the other groups. Sex offenders were found to be a unique group that does not fit in the “classic offenders” category. They were found to have low aggression levels and high anxiety levels and their scores on PD-4 and ASP scales were low compared with the other groups. The traffic group was characterized with typically low levels of anxiety and high levels of physical aggression. This group also obtained high scores on ASP scale and the measure that examined confrontation with authority figures. Finally, study findings did not indicate characteristics that typify the nonspecific violence offenses. [ABSTRACT FROM PUBLISHER]

Keratinocytes, the dominant cell type in the melanoma microenvironment during tumor initiation, exhibit diverse effects on melanoma progression. Using a zebrafish model of melanoma and human cell co-cultures, we observed that keratinocytes undergo an Epithelial-Mesenchymal Transition (EMT)-like transformation in the presence of melanoma, reminiscent of their behavior during wound healing. Surprisingly, overexpression of the EMT transcription factor Twist in keratinocytes led to improved overall survival in zebrafish melanoma models, despite no change in tumor initiation rates. This survival benefit was attributed to reduced melanoma invasion, as confirmed by human cell co-culture assays. Single-cell RNA-sequencing revealed a unique melanoma cell cluster in the Twist-overexpressing condition, exhibiting a more differentiated, less invasive phenotype. Further analysis nominated homotypic jam3b-jam3b and pgrn-sort1a interactions between Twist-overexpressing keratinocytes and melanoma cells as potential mediators of the invasive restraint. Our findings suggest that EMT in the tumor microenvironment (TME) may limit melanoma invasion through altered cell-cell interactions.