TY - JOUR T1 - CD95 and TNFα-induced Apoptosis in Liver Metastases of Colorectal Carcinoma JF - In Vivo JO - In Vivo SP - 653 LP - 657 VL - 24 IS - 5 AU - HANS-UDO KASPER AU - ELISABETH KONZE AU - MICHAEL KERN AU - DIRK LUDGER STIPPEL Y1 - 2010/09/01 UR - http://iv.iiarjournals.org/content/24/5/653.abstract N2 - Background: Therapeutic options in patients with metastatic colorectal cancer are still limited. As apoptosis contributes to the overall sensitivity to radiotherapy or chemotherapy, a better understanding of the apoptotic process in metastatic tumour tissues is necessary. Materials and Methods: Precision cut tissue slices (PCTS) of three human liver metastases were used to investigate the effect of activating CD95 antibodies (concentrations: 0.1 μg/ml, 1 μg/ml and 1 μg/ml and 1 μg/ml actinomycin D) as well as TNFα (concentrations 1 ng/ml; 10 ng/ml and 10 ng/ml and 1 μg/ml actinomycin D) directly in tumour tissue after 6 h, 12 h and 24 h. The apoptotic effect was assessed immunohistochemically. Results: Activating CD95 antibodies combined with actino-mycin D led to a significant increase in apoptosis after 12 h. Using TNFα at a high dosage, a significant increase in the apoptosis rate was observed after 6 h and after 12 h in all dosage groups. Conclusions: PCTS can be used to investigate the effect of different apoptotic signals directly in human tumour tissues. TNFα is able to effectively induce apoptosis in liver metastases of colorectal carcinoma. Thus, the extrinsic pathway of apoptosis may be a promising target in the development of new therapeutic approaches. ER -