CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells.

The molecular alterations in tumour cells leading to resistance towards apoptosis induced by CD95 and TRAIL-receptors are not fully understood. We report here that the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kappaB. Inhibition of protein kinase C by Gö6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kappaB by anti-CD95 and TRAIL. Similarly, inhibition of NF-kappaB by MG132 or by transient transfection with a dominant negative mutant of IkappaBalpha restored the responsiveness of PancTuI cells to both death ligands. In the CD95 and TRAIL-sensitive cell line Colo357 the induction of protein kinase C and NF-kappaB following activation of CD95 and TRAIL-R was very moderate compared with PancTuI cells. However, pre-incubation of these cells with PMA strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together, we show that activation of protein kinase C operates directly in a death receptor-dependent manner in PancTuI cells and protect pancreatic tumour cells from anti-CD95 and TRAIL-mediated apoptosis by preventing the loss DeltaPsim and Cytochrome c release as well as by induction of NF-kappaB.

[Fracture of the tibial shaft--still a traumatology problem?]. / Die Unterschenkelschaftfraktur--noch immer ein traumatologisches Problem?

Diaphyseal fractures of the lower leg have continued to hold a special position in terms of incidence, type, severity, and frequency of typical complications as well as healing disorders. Despite general consensus regarding fracture healing and major factors of influence, there still is discrepancy of opinions and recommendations, in the context of pathophysiology, mechanics, and therapy. All in all, 302 fresh fractures and 134 cases of delayed healing or pseudoarthrosis in the diaphyseal region were treated, between 1971 and 1985. It has been the authors' experience that conservative treatment, according to the classical school, should be applied whenever possible. The trend in surgery, primarily for open fractures, is towards adequately dimensioned fixateur externe. Accurately defined minimum instability and healing with callus formation are nowadays appreciated and preferred. The fibula-ligament-membrane-complex may assume great importance to instable or defective forms of tibial fractures. Experimental and clinical investigations are likely to suggest that, depending on the individual case, the fibula should be included in the overall therapeutic concept, when it comes to impaired or delayed healing and pseudoarthrosis.

[Amputation after traumatic lesion of the popliteal artery-avoidable or inevitable? (author's transl)]. / Amputation nach traumatischer Läsion der A. poplitea--vermeidbar oder zwangsläufig?

Each serious injury of the joint of the knee involves the possibility of an additional lesion of the popliteal artery. Among the arterial injuries the traumatic lesions of the popliteal artery with a frequency of up to 20% are of great importance. Failure to recognize or estimate them correctly may result in a high rate of amputations. In addition, three own cases were critically analysed.