Acute infections as a means of cancer prevention: opposing effects to chronic infections?

PURPOSE: Epidemiological studies have found an inverse association between acute infections and cancer development. In this paper, we review the evidence examining this potentially antagonistic relationship. METHODS: In addition to a review of the historical literature, we examined the recent epidemiological evidence on the relationship between acute infections and subsequent cancer development in adult life. We also discuss the impact of chronic infections on tumor development and the influence of the immune system in this process. RESULTS: Exposures to febrile infectious childhood diseases were associated with subsequently reduced risks for melanoma, ovary, and multiple cancers combined, significant in the latter two groups. Epidemiological studies on common acute infections in adults and subsequent cancer development found these infections to be associated with reduced risks for meningioma, glioma, melanoma and multiple cancers combined, significantly for the latter three groups. Overall, risk reduction increased with the frequency of infections, with febrile infections affording the greatest protection. In contrast to acute infections, chronic infections can be viewed as resulting from a failed immune response and an increasing number have been associated with an elevated cancer risk. CONCLUSION: Infections may play a paradoxical role in cancer development with chronic infections often being tumorigenic and acute infections being antagonistic to cancer.

Dr William Coley and tumour regression: a place in history or in the future.

Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.

Spontaneous regression: a hidden treasure buried in time.

Spontaneous tumor regression is a phenomenon that has been observed for hundreds, if not thousands of years. Although the term spontaneous implies 'without apparent cause', a review of case reports over the last several hundred years demonstrates that regression generally coincides with acute infections. Observations of this non-specific effect led to the emergence of active cancer immunotherapies by the 1700s. By the 1890s, William Coley refined this approach with a bacterial vaccine which, when administered properly, could induce complete regression of extensive metastatic disease. Unfortunately, after Coley's death, his vaccine and technique fell into obscurity. Modern approaches to treatment have reduced the occurrence of spontaneous regressions. Aseptic techniques and antibiotics significantly reduce postoperative infections, while chemotherapy and radiation impair immune activation even when an infection does occur. More than a century after its inception, Coley's vaccine and aggressive approach to treatment may still be one of most effective immunotherapies for cancer.

Elemental and radioactive analysis of commercially available seaweed.

Edible seaweed products have been used in many countries, specifically Japan, as a food item. Recently these products have become popular in the food industry because of a number of interesting medicinal properties that have been associated with certain edible marine algae. Very little control exists over the composition of these products, which could be contaminated with a number of agents including heavy metals and certain radioactive isotopes. Fifteen seaweed samples (six local samples from the coast of British Columbia, seven from Japan, one from Norway and one undisclosed) were obtained. All samples were analyzed for multiple elements, using ICP mass spectrometry and for radioactive constituents. It was found that six of eight imported seaweed products had concentrations of mercury orders of magnitude higher than the local products. Lead was found at somewhat higher concentrations in only one local product. Laminaria japonica had the highest level of iodine content followed by Laminaria setchellii from local sources. Only traces of cesium-137 were found in a product from Norway and radium-226 was found in a product from Japan. Arsenic levels were found to be elevated. In order to estimate the effect of these levels on health, one needs to address the bioavailability and the speciation of arsenic in these samples.

Hypothesis: iodine, selenium and the development of breast cancer.

BACKGROUND: In this paper we examine some of the evidence linking iodine and selenium to breast cancer development. Seaweed is a popular dietary component in Japan and a rich source of both of these essential elements. We hypothesize that this dietary preference may be associated with the low incidence of benign and malignant breast disease in Japanese women. In animal and human studies, iodine administration has been shown to cause regression of both iodine-deficient goiter and benign pathological breast tissue. Iodine, in addition to its incorporation into thyroid hormones, is organified into anti-proliferative iodolipids in the thyroid; such compounds may also play a role in the proliferative control of extrathyroidal tissues. Selenium acts synergistically with iodine. All three mono-deiodinase enzymes are selenium-dependent and are involved in thyroid hormone regulation. In this way selenium status may affect both thyroid hormone homeostasis and iodine availability. CONCLUSION: Although there is suggestive evidence for a preventive role for iodine and selenium in breast cancer, rigorous retrospective and prospective studies are needed to confirm this hypothesis.

Macrophage-tumor cell associations: a factor in metastasis of breast cancer?

In human breast carcinomas tumor cells and macrophages are often proximal. We previously reported on the relationship between tumor cell growth and macrophage concentration and report here on the possible involvement of macrophages in the metastatic process. We hypothesize that during the initial stages of metastasis, tumor cells are likely to encounter macrophages and form aggregates. Using a cell culture method that encourages cellular interactions, we found aggregates involving macrophages. Macrophages partly or completely surround other cell types without any apparent ill effect. Units involving macrophages and tumor cells would possess many properties necessary for invasion, which is a normal process for macrophages. Properties such as motility and production of specific enzymes necessary to traverse the extracellular matrix, basement membrane, and endothelial cell barriers may provide an advantage for tumor cells. Physical support and protection from immune recognition during transport of the tumor cell through the vascular system may also be enhanced, and paracrine growth stimulation and angiogenic activity may be provided at the new metastatic site. Verification of these observations in vivo could lead to new directions for limiting breast cancer metastasis.