Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine

Basal cell carcinoma, medulloblastoma, rhabdomyosarcoma and other human tumours are associated with mutations that activate the proto-oncogene Smoothened (SMO) or that inactivate the tumour suppressor Patched (PTCH). Smoothened and Patched mediate the cellular response to the Hedgehog (Hh) secreted protein signal, and oncogenic mutations affecting these proteins cause excess activity of the Hh response pathway. Here we show that the plant-derived teratogen cyclopamine, which inhibits the Hh response, is a potential 'mechanism-based' therapeutic agent for treatment of these tumours. We show that cyclopamine or synthetic derivatives with improved potency block activation of the Hh response pathway and abnormal cell growth associated with both types of oncogenic mutation. Our results also indicate that cyclopamine may act by influencing the balance between active and inactive forms of Smoothened.     

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.     

Desoxypatulinic acid from a patulin-producing strain ofPenicillium patulum

Zusammenfassung Aus Kulturlösungen vonPenicillium patulum Bainier wurde neben Patulin die Desoxypatulinsäure isoliert und identifiziert.     

Noradrenolutin

Zusammenfassung Herstellung und einige Eigenschaften von kristallinem Noradrenolutin (5,6-Dioxyindoxyl), dem gelbgrün fluoreszierenden Oxydationsprodukt von Noradrenalin, werden beschrieben.     

The electron-transfer absorption of substituted benzenes

Zusammenfassung Eine allgemeine Methode für die Berechnung der Hauptabsorptionsbande benzolischer Carbonylverbindungen wird zur Diskussion gestellt.     

Carbon compounds in Apollo 11 lunar samples

Are they entrapped solar wind particles, meteoritic or cometary contributions, remnants of a primordial atmosphere or products of the degassing of the Moon ?