Does cryosurgery of tumor tissue cause endotoxin tolerance through an inflammatory response?
These experiments confirm the hypothesis that cryosurgery leads to a systemic inflammatory response. This reaction can lead to the inhibition of tumor growth. Administration of LPS after cryosurgery does not lead to an extra anti-tumor response; animals appear to become endotoxin tolerant. Adversely, when LPS is administered together with cryosurgery, the animals are extremely sensitive to LPS. These findings are in accordance with the clinical observation of cryoshock after cryoablation of liver metastases.
The induction of Ins2 by GW8510 occurred through p53 in a JNK- and p38-dependent manner. These results implicate p53 activity in modulation of Ins2 expression levels in pancreatic alpha cells, and point to a potential approach toward using small molecules to generate insulin in an alternative cell type.