The First Validated Nomogram to Predict 30-day Mortality following Surgery for Small Bowel Obstruction 5 2 Randomized Assessment of Alcohol Consumption with Computerized Alcohol Screening and Brief Intervention for Adult Emergency Patients

Immunotherapy of malignant tumors is making progress towards improving patient survival with some cancers. The Herceptin antibody which targets a critical growth factor receptor on breast cancers has significantly improved survival in those women whose tumors over-express that receptor. Not only does Herceptin receptor blockade interfere with a key growth factor signaling pathway on the tumor cells, but it permits antibody-dependent cell-mediated cytotoxicity. This represents a dual-purpose anti-tumor effect. Purpose: We found that glioma BK (gBK) mRNA and protein were highly expressed in human small cell lung cancers (SCLC) patients at their time of death, while little expression of gBK was present in the initial SCLC. This empirical finding suggests that gBK expression is a sign of progression towards the terminal SCLC stages. Experimental Design: Human surgical and autopsy samples of SCLC were studied along with SCLC cell lines using real time PCR, antibody staining and functional assays. Human cytolytic T lymphocytes (CTL) showed the translation potential of this molecule. Results: SCLC cell lines responded to specific BK channel activators by swelling. This response was specifically inhibited by using Iberotoxin, indicating that functional BK channels were present. Five-hour exposure to BK channel activators induced cell death within SCLC cell lines. Human CTL generated against two epitopes found within the gBK region killed HLA-A2+ SCLC cells, while HLA-A2+ human embryonic kidney cells that are gBK-negative were not killed. The exposure of SCLC to interferon-? (IFN-?) increased the expression of HLA-A2 on SCLC; these treated cells were killed better than those cells not treated with IFN-?. IFN-? treated SCLC cells diminished gBK protein expression. Prolonged incubation with IFN-? slowed the in vitro growth of the SCLC cells, suggesting a novel method of inhibiting tumor growth. Conclusions: Immunotherapy of SCLC using gBK could be designed around the idea of “immuno-preventing” the terminal phases of this cancer. The lymphocyte mediated effector function may even be mediated through a novel non-cytolytic dependent process.