Spotlight

Abstract

Yang et al., pp. 495–499 The anti-diabetic drug troglitazone (TGZ), a PPAR-gamma agonist, enhances in vivo tumor formation in mouse models of human colon cancer, independent of pre-existing mutational events. Over a period of 6 months, the authors fed the troglitazone (TGZ) to two mouse strains one wild-type and one predisposed to intestinal genetically altered strain that rarely develops colonic tumors. They observed an increase in colonic tumor development in both strains. Effects of PPAR-gamma agonists on colon cancer remain highly controversial. Although PPAR-gamma activation has been shown to inhibit prostate and breast cancers, PPAR-gamma agonists have been shown to inhibit colon cancer growth as well as promote it, in different experiments. In the current study, researchers observed an increase in flat colonic adenomas, believed to be particularly aggressive. The results support the view that activated PPAR-gamma promotes colon cancer in mutant mice and demonstrate for the first time that normal mice also respond the same way. Normal mice fed TGZ for 6 months developed aggressive colon tumors. Zelmanowicz et al., 599–605 Familial aggregation of cervical cancer has been reported in various studies, suggesting that family history increases risk of disease. Yet it remains unclear whether familial aggregation results from genetic predisposition or shared environmental exposure and lifestyle factors. The current study examined data from two large case-control studies, one in the United States and one in Costa Rica, and concluded that a family history of cervical cancer in first-degree relatives appears to be associated with increased risk for cervical intraepithelial neoplasia type 3 and squamous cell carcinoma of the cervix, but not for adenocarcinomas. In the Costa Rican study, the association persisted in analyses limited to women known to be exposed to oncogenic types of HPV, indicating that shared environmental risk does not fully explain the association.Whereas the nature of familial aggregation studies makes it difficult to distinguish between the effects of genetic and shared environmental factors, previous work showing stronger familial effects among biological relatives compared with adoptive or half-relatives provides an important context in which to place these new findings. Evidence of an association between HLA polymorphisms and cervical cancer risk, previously reported, also serves to strengthen the case for the involvement of genetic factors. Tanaka et al., pp. 624–633 Dendritic cells can be used to increase the effectiveness of targeted heat in battling tumors, according to a new study on melanoma in rats. In earlier work, Tanaka and colleagues showed that heat treatment could be targeted to tumor cells in rats with minimal damage to normal cells. They used magnetic nanoparticles that generate heat in an alternating magnetic field and developed liposomes that preferentially concentrated the nanoparticles in tumor cells. Upon application of the magnetic field, the heat that was generated shrank the tumors containing the nanoparticles. This hyperthermia system also induced antitumor immunity, mediated by HSP70, which immunizes the rats upon release from the dying tumor cells. The researchers suspected that a dendritic cell-based vaccine could be a powerful weapon against malignant tumors if the cells can be induced to take up the antigen efficiently. As dendritic cells mature, they lose the ability to take up antigens, and it can be difficult to obtain enough tumor antigen from the patient. One way around this problem is to inject immature dendritic cells into the tumor. Hence, the authors decided to try injecting immature dendritic cells into tumors releasing HSP70 after heat treatment in hopes that this would magnify the immune response. They observed that the heated tumor cells induced dendritic cell maturation, and that the injection of immature dendritic cells in combination with the targeted heat induced antitumor immunity, suggesting that the combination approach could be of value to patients with advanced malignancies.