ABSTRACT
In cancer therapy vastly different kinds of treatment regimens, but as a rule scientifically validated and reviewed, play a central role dependent on the tumor entity. Besides the options of schoolbook medicine complementary, alternative and supportive treatment options are becoming more frequently used in routine clinical practice. Numerous concepts and agents, partly verified in studies and partly based on empirical experiences are being applied. It is our intention to give a survey of the most common agents and concepts and to point out the risks and capabilities.
Subject(s)
Complementary Therapies/methods , Urogenital Neoplasms/therapy , Combined Modality Therapy , Complementary Therapies/adverse effects , Humans , Palliative Care/methods , Phytotherapy/adverse effects , Phytotherapy/methods , Plant Extracts/administration & dosage , Plant Extracts/adverse effects , Prognosis , Urogenital Neoplasms/pathology , Viscum albumABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are highly resistant to treatment due to changes in various signalling pathways. CK1 isoforms play important regulatory roles in these pathways. AIMS: We analysed the expression levels of CK1 delta and epsilon (CK1delta/in) in pancreatic tumour cells in order to validate the effects of CK1 inhibition by 3-[2,4,6-(trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261) on their proliferation and sensitivity to anti-CD95 and gemcitabine. METHODS: CK1delta/in expression levels were investigated by using western blotting and immunohistochemistry. Cell death was analysed by FACS analysis. Gene expression was assessed by real-time PCR and western blotting. The putative anti-tumoral effects of IC261 were tested in vivo in a subcutaneous mouse xenotransplantation model for pancreatic cancer. RESULTS: We found that CK1delta/in are highly expressed in pancreatic tumour cell lines and in higher graded PDACs. Inhibition of CK1delta/in by IC261 reduced pancreatic tumour cell growth in vitro and in vivo. Moreover, IC261 decreased the expression levels of several anti-apoptotic proteins and sensitised cells to CD95-mediated apoptosis. However, IC261 did not enhance gemcitabine-mediated cell death either in vitro or in vivo. CONCLUSIONS: Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.
