Frances S. Kim

Hyperthermia induces heat-shock protein expression, reduces pancreatic injury, and improves survival in necrotizing pancreatitis.

Heat-shock proteins (HSPs) function in the cellular response to injury. Increased expression of these proteins was first described in response to hyperthermia, although their production may be prompted by a variety of metabolic insults. HSPs protect cellular proteins from degradation. The self-limited pancreatitis induced by hyperstimulation with supramaximal doses of cerulein is accompanied by increased HSP expression. It may be that HSPs serve a protective function in pancreatitis. We hypothesized that hyperthermia-induced production of HSP-70 would improve survival in a lethal murine model of necrotizing pancreatitis. Necrotizing pancreatitis was induced in two groups of 30 female Swiss Webster mice by feeding them a choline-deficient diet supplemented with 0.5 g% ethionine (CDE) for 72 hours. Immediately before initiation of the CDE diet, the core body temperatures of the mice in the experimental group were elevated to 42°C for 12.5 minutes. Twenty mice from each group were killed after 24 hours. Pancreata were harvested, and pancreatic proteins were extracted from half of the pancreata. HSP-70 was assessed according to a standard Western blotting protocol. The remaining pancreata were used to make histologic comparisons. Serum interleukin 6 and tumor necrosis factor-&agr; were determined by enzyme-linked immunosorbent assay (ELISA). Survival was determined by observation of the remaining mice. HSP-70 was expressed in pancreatic protein from all mice exposed to hypothermia but in none of the mice subjected to the CDE diet alone. Mortality was significantly reduced in mice pretreated with hyperthermia compared with control mice (p < 0.05). Survival in the hyperthermia group was 80%, whereas in the control group it was 30%. Hyperthermia resulted in expression of pancreatic HSP-70 in mice. Hyperthermia also reduced mortality in this lethal murine model of necrotizing pancreatitis. It is plausible that a causal relationship exists between HSP-70 production and improved survival in this model.

Irradiation-induced up-regulation of Fas in esophageal squamous cell carcinoma is not accompanied by Fas ligand-mediated apoptosis.

Fas (APO‐1) induces apoptosis after binding Fas ligand (FasL). Evidence suggests that tumors may use this interaction to evade the host immune response. Fas/FasL expression has not been reported in esophageal cancer. We hypothesized that Fas expression would render esophageal cancer cells susceptible to Fas ligation and that irradiation of the cells would increase Fas expression.

B-cell leukemia protein-2 and peptide YY chemotherapy resistance in colon cancer

BACKGROUND Inhibition of apoptosis may allow cells with drug-induced damage to escape programmed cell death. The bcl-2 protein inhibits apoptosis and bcl-2 overexpression has been associated with drug resistance. It is our hypothesis that higher levels of bcl-2 expression will be seen in colon cancer cells resistant to PYY treatment. METHODS Caco2 and HCT116 colon cancer cells were treated with 2 microM PYY for 24 hours. Protein was extracted from cells surviving PYY treatment; bcl-2 expression was measured by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. RESULTS Caco2 and HCT116 cells surviving PYY treatment demonstrated increased bcl-2 from 20.54+/-2.7 to 28.63+/-2.20 units/mL (P <0.05) and 21.98+/-1.28 to 29.32*+/-2.26 units/mL, respectively. CONCLUSIONS Increased expression of bcl-2 is seen in a population of colon cancer cells resistant to PYY. Hence, bcl-2 may protect neoplastic cells from apoptosis; its levels may be useful in predicting chemotherapy response and in selecting appropriate drug regimens.