MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas

Vorgestalten und Selbstkorrumpierung auf dem Weg zum Affektdelikt

Der Beitrag erörtert, aufbauend auf früheren Überlegungen, die Begriffe Vorgestalt und Selbstkorrumpierung im Kontext der psychiatrischen Begutachtung affektiv akzentuierter Delikte. In beiden Fällen handelt es sich um komplexe psychopathologische Phänomene, die auf den Beurteilungsebenen des Querschnitts (Befund zu einem bestimmten Zeitpunkt) und Längsschnitts (Entwicklung über die Zeit bis hin zur Tathandlung) erfasst werden müssen. Vorgestalten meint hier kognitiv mehr oder weniger strukturierte, imaginierte Vorwegnahmen wesentlicher Elemente eines später real eingetretenen, stark affektiv geprägten Tatzusammenhangs. Sie können im Einzelfall für oder gegen die Annahme einer erheblich eingeschränkten Steuerungsfähigkeit sprechen. Welche Indikatorfunktion sie haben, hängt vom psychopathologischen Kontext ab. Der nicht wertfreie Begriff Selbstkorrumpierung bezeichnet eine komplexe, nicht leicht erkennbare Alteration des individuellen Wertgefüges im (möglicherweise jahrelangen) Vorfeld der Tat. Auch dieses Phänomen kann für die forensische Beurteilung einer affektiv akzentuierten Straftat hilfreich sein, sofern es kritisch reflektiert verwendet wird. Der psychopathologischen Perspektive kommt in dieser Debatte eine kardinale Bedeutung zu. Dies gilt freilich nur dann, wenn die Psychopathologie sich in ihrem Selbstverständnis klar jenseits der bloßen Symptomerhebung bewegt und dabei die wissenschaftstheoretische und wissenschaftshistorische Perspektive aktiv einbezieht. This paper addresses imaginative preoccupations (“Vorgestalten”) and mechanism of self-corruption prior to a crime of passion (“Affektdelikt”). Both are complex psychopathological issues which have to be evaluated for cross-sectional and longitudinal dimensions. Imaginative preoccupations indicate cognitive and affective precursors of significant elements of the later aggressive criminal behaviour. Depending on the given psychopathological context, they may be indicative for or against diminished criminal responsibility. Self-corruption is definitely a (negatively) value-laden term and addresses a gradual alteration of the individual value system prior to the actual aggressive behaviour which can, but does not necessarily have to be of forensic relevance. Generally speaking, the psychopathological perspective is of major importance here, if and only if psychopathology clearly reaches beyond mere description of symptoms and systematically includes epistemology and conceptual history of psychiatry