Lessons Learned from a Devil
O'Neill etal., pp. 1637–1642
The Tasmanian devil, the largest living carnivorous marsupial, is an iconic animal in Australia. The black, sturdy, dog-like animal serves as the symbol of the Tasmanian National Parks and Wildlife Service and has appeared on commemorative Australian two-dollar coins. The devil is known for its ferocious appetite and fierce fighting habits. Previously considered relatively common, it is now listed as an endangered species; its original population declined by 70–90% over the last 15 years due to a mysterious face tumor called the Tasmanian devil facial tumor disease (DFTD).
In this article, Iain O'Neill reviews the origins of DFTD as the prototype of a transmittable noninfectious tumor. He lays out the evidence that the relative genetic isolation on the Tasmanian island plays a critical role in the inability of the devil's immune system to fight off transmitted tumor cells. DFTD was first reported in 1996 and is a disfiguring facial and oral malignancy with 100% mortality. Histologically, an undifferentiated neuroendocrine tumor, it kills affected animals by impairing feeding but also through regional and systemic metastasis. O'Neill summarizes the evidence leading to the conclusion that transmission of clonal tumor cells occurs through fighting and facial bites and that the devil's reduced MHC diversity is to blame for the rapid spread of the deadly disease. He points out that molecular studies of DFTD may serve to elucidate rare settings of tumor transmission in humans, such as transplantation tumor transmission or cell trafficking at the fetal-maternal interface.
Prostate Cancer Incidence Decreased by Screening
Kilpeläinen et al., pp. 1699–1705
By Anne Forde
The overall benefits of prostate cancer screening programs remain controversial. Preliminary findings of a large European trial–ERSPC–has shown a decrease in prostate cancer mortality of 20%, whereas a US-based trial showed no difference.
In this report, the authors analyzed the incidence rates in a large population-based prostate cancer trial in Finland, which forms part of ERSPC. This prospective randomized screening trial comprised three rounds of screening and was conducted over 12 years with over 80,000 men enrolled. Men in the screening arm of the study were invited for prostate-specific antigen (PSA) screening every 4 years and those in the control arm received no intervention.
The total cumulative incidence of prostate cancer was 8.3% in the screened group and 5.8% in the control group (p < 0.001). Interestingly, the cumulative incidence of localized cancer was 5.3% in the screened versus 3% in control groups. Importantly, this phenomenon was reversed for advanced prostate cancer, where the cumulative incidence was found to be 1% in the screened group and 1.4% in the control group.
The protocol used in the study used a relatively higher PSA cut off of 4 ng/ml. The authors concede that their study overdiagnosed a proportion of low-grade cancers, which is not without consequence. However, a drop in the cumulative incidence of advanced prostate cancer of one third in the screened group is the hallmark of a successful screening program.
New Electric Therapy Can Safely Destroy Melanoma in Mice
Nuccitelli et al., pp. 1727–1736
Nanosecond pulse electric field (nsPEF) therapy for experimental tumor models has been around for several years. It offers the substantial benefits of inducing apoptosis and only affecting the tissues placed between the delivery electrodes.
Previously these authors had shown that one to three nsPEF treatments could eliminate melanomas in immune-competent mice. In this report, Nuccitelli et al., raise the stakes by using athymic mice, whose immune system cannot halt tumor growth. They also use newly designed suction electrodes that are more compatible with human skin and employed a short, but high pulse length treatment.
NsPEF treatment was optimized for electrode configuration, pulse number, amplitude and frequency. After one 6-min nsPEF treatment, the fluorescent signal in mice bearing GFP melanomas could no longer be detected 24 hours later. Tumors shrank and disappeared within 5–10 days. Importantly, the changes were highly localized: capillaries narrowed, melanoma and epidermal cells shrank in the treated tissue but there was no damage in the epidermis or capillaries of the neighboring tissue. The authors used the highest pulse application possible to minimize the treatment time but always kept the temperature below 40°C. All in all, the treatment eliminated all 17 melanomas in 4 mice.
“… the treatment eliminated all 17 melanomas in 4 mice.”
These results contribute to ongoing efforts to develop nsPEF technology suitable for humans. The suction electrodes developed in this study are more applicable to human use and the parameters used offers excellent efficacy and safety. NsPEF therapy is not cell specific and therefore has a high potential, though its use in internal body tumors still has a long way to go.