RT Journal Article
SR Electronic
T1 CD95 and TNFα-induced Apoptosis in Liver Metastases of Colorectal Carcinoma
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 653
OP 657
VO 24
IS 5
A1 HANS-UDO KASPER
A1 ELISABETH KONZE
A1 MICHAEL KERN
A1 DIRK LUDGER STIPPEL
YR 2010
UL http://iv.iiarjournals.org/content/24/5/653.abstract
AB 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.