Immunotherapy of murine prostate cancer using whole tumor cells killed ex vivo by herpes simplex viral thymidine kinase/ganciclovir suicide gene therapy.

Whole cell cancer vaccines are currently under clinical evaluation. Their immunogenicity may depend on the mode of death of the vaccine cells prior to uptake by professional antigen-presenting cells and crosspriming of T cells. Destruction of tumor in vivo by genetic prodrug activation therapy leads to a marked local and systemic immune response, local T-cell infiltration and the establishment of T-cell memory. We postulated that this immunostimulation may be due to induction of danger signals and the inherent immunogenicity of products of HSVtk/ganciclovir kill. Using established models of murine prostate cancer, we have evaluated the efficacy of anti-tumor vaccines comprising irradiated allogeneic or autologous whole cells expressing HSVtK, which are first killed in vitro by prodrug activation using ganciclovir. HSVtk/ganciclovir-induced cell kill was through the induction of apoptosis. The vaccine was found to be effective in both models and superior to traditional irradiated whole tumor cells even after single doses. Protection against tumor challenge was associated with marked proliferative and Th1 cytokine responses. This approach would be applicable clinically in terms of ease of vaccine production, safety, storage and avoidance of potential toxicities of in vivo gene transfer.

Attitudes of contemporary parents toward behavior management techniques used in pediatric dentistry.

PURPOSE: The objective of this study was to examine parental attitudes toward behavior management techniques currently used in pediatric dentistry. METHODS: Fifty-five parents viewed videotaped scenes of 8 behavior management techniques being used during actual pediatric dental treatment. The 8 techniques shown were: (1) tell-show-do; (2) nitrous oxide sedation; (3) passive restraint; (4) voice control; (5) hand-over-mouth; (6) oral premedication (sedation); (7) active restraint; and (8) general anesthesia. Parents rated their acceptance of each technique using a visual analogue scale (VAS). RESULTS: Forty-six parents completed survey forms for analysis. Tell-show-do was rated as the most acceptable technique, followed (in order of decreasing acceptance) by: (1) nitrous oxide sedation; (2) general anesthesia; (3) active restraint; (4) oral premedication; (5) voice control; (6) passive restraint; and (7) hand-over-mouth. The following groups emerged with statistically similar means: (1) tell-show-do and nitrous oxide sedation; (2) nitrous oxide sedation, general anesthesia, and active restraint; and (3) general anesthesia, active restraint, oral premedication, and voice control. Hand-over-mouth and passive restraint were rated as the least acceptable techniques, and the ratings for both techniques were significantly different from all other techniques and from each other. Overall, hand-over-mouth was the least acceptable technique. Acceptance of each behavior management technique was not related to parental age, gender, education level, or social status. CONCLUSIONS: The mean parental acceptance rating was in the acceptable range for all behavior management techniques examined in this study except for hand-over-mouth. General anesthesia was ranked as the third most acceptable technique. This high level of acceptance of general anesthesia compared to earlier studies may suggest that parental acceptance of this technique is increasing.

Large staghorn calculus presenting as a loin abscess and complicated by an abdominal aortic aneurysm.

We present the case and radiologic images of an 85-year-old woman who presented with a left loin abscess secondary to a left staghorn calculus and a nonfunctioning left kidney. We examined the rationale behind the eventual decision to pursue conservative treatment in the form of incision and drainage rather than nephrectomy. This was because of the patient's frailty and the presence of an abdominal aortic aneurysm in close proximity to the left kidney. The radiologic images are of great quality and interest because they display the pathologic findings very clearly. Our brief case report outlines the decision-making process.

Heated tumour cells of autologous and allogeneic origin elicit anti-tumour immunity.

Vaccination with established tumour cell lines may circumvent the problem of obtaining autologous tumour cells from patients, but may also need immunological adjuvants. Up-regulation of heat shock proteins within tumour cell vaccines has resulted in increased immunogenicity in some models, but this has yet to be demonstrated for allogeneic (MHC-disparate) cell vaccines. This was investigated here using a rat model for prostate tumour cell vaccination. Heating of tumour cells (42 degrees C, 1 h) elicited significant increases in HSP70 expression. Vaccination with heated autologous PAIII cells elicited protection against PAIII challenge in 60% of rats >50 days compared to 0% with unheated vaccine and was associated with an increased Th1 (IFNgamma) immune response. Heated allogeneic MLL cells elicited significant protection against PAIII challenge, in contrast to unheated cells. The principle was confirmed in two mouse models, although the allogeneic melanoma vaccine K1735 elicited the best protection when heated and administered mixed with autologous dendritic cells. Thus, while heating of vaccine cells in some models is highly beneficial, and is a means of enhancing immunogenicity without genetic modification or inclusion of potentially toxic adjuvants, additional immune enhancement may be required.