In this study we sought to clarify the role of the proapoptotic potential of mitochondria in the death pathway emanating from the TRAIL (APO-2L) and CD95 receptors in pancreatic carcinoma cells. We focused on the role of the Bcl-2 family member Bcl-XL, using three pancreatic carcinoma cell lines as a model system, two of which have high (Panc-1, PancTuI) and one has low (Colo357) Bcl-XL expression. In these cell lines, the expression of Bcl-XL correlated with sensitivity to apoptosis induced by TRAIL or anti-CD95. Flow cytometric analysis revealed cell surface expression of TRAIL-R1 and TRAIL-R2 on PancTuI and Colo357, and TRAIL-R2 on Panc-1 cells. In Colo357 cells retrovirally transduced with Bcl-XL, caspase-8 activation in response to treatment with TRAIL or anti-CD95 antibody was not different from parental cells and EGFP-transfected controls, however, apoptosis was completely suppressed as measured by the mitochondrial transmembrane potential deltapsim, caspase-3 activity (PARP cleavage) and DNA-fragmentation. Inhibition of Bcl-XL function by overexpression of Bax or administration of antisense oligonucleotides against Bcl-XL mRNA resulted in sensitization of Panc-1 cells to TRAIL and PancTuI cells to anti-CD95 antibody-induced cell death. The results show that Bcl-XL can protect pancreatic cancer cells from CD95- and TRAIL-mediated apoptosis. Thus, in these epithelial tumour cells the mitochondrially mediated 'type II' pathway of apoptosis induction is not only operative regarding the CD95 system but also regarding the TRAIL system.

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Summary. From cultures ot Streptomyces viridochvoinogenes a new antibiotic, phosphinothricylalanyl-alanine, has been isolated. The new amino acid phosphinothricin is 2-amino-4-methylphosphino-butyric acid, its structure is confirmed by synthesis.The tripeptide is highly active against Gram-positive and Granz-negative bacteria and against thc fungus Botrytis cinerea. Phosphinothricin is an active glutamine synthetase inhibitor.

The use of novel polysiloxanes as stationary phase carrying chiral groups enables the separation of most amino acid enantiomers in a much shorter time than ever reported previously. Phases of this type exhibit very low volatility and high thermal stability and may be used in routine analysis with open tubular columns ant temperatures of at least 175 degrees C. Most protein amino acids are separated in a temperature program between 90 and 175 degrees C, thus obviating the need for multiple injections. Resolution factors are somewhat lower than those of other diamide phases containing the L-valine t-butyl-amide group, but are sufficient for resolution of almost all protein amino acid enantiomers.

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