Combined Radiation and Vaccine Therapy Can Halt Tumor Proliferation

NCI researchers have shown that sub-lethal doses of radiation administered in combination with tumor-specific vaccines can reduce tumor size and stimulate immune system-related cells. In the June 15 Cancer Research, a team of NCI scientists led by Drs. Mala Chakraborty and James Hodge demonstrated that exposure to low amounts of radiation, either by single or multiple doses, can augment the effects of a tumor-specific vaccine regimen.

Recent research has shown that sub-lethal amounts of radiation can be used to stimulate host immune system cells without causing serious tissue damage. Vaccine therapy, currently only in experimental stages, also focuses on generating a greater host immune response to cancer.

Using mouse models to assess several endpoints, including the expression of proteins in tumors and the rise of T cells within the tumor site, scientists reported that at 8 days following tumor transplant, mice that received vaccine or radiation therapy alone did not have significant tumor reduction. Mice that received combination vaccine and radiation treatment demonstrated a marked decline in tumor growth as well as volume. When single-dose radiation therapy was compared with fractionated dose radiation therapy (both in conjunction with the vaccine), approximately 50 percent of the mice were cured of tumor. This combination therapy "may induce far more effective anti-tumor responses than those seen using either modality alone," the authors noted.

Smoking Affects Genes in Bronchial Cells

Researchers have detected 97 genes in bronchial airway cells that alter their expression levels when exposed to cigarette smoke. They discovered that while most of these altered genes revert back to normal expression 2 years after an individual stops smoking, some genes remain at altered levels even 30 years after smoking cessation. These findings, reported in the July 6 Proceedings of the National Academy of Sciences, may explain why former smokers' risk of cancer remains high many years after quitting.

The team of the Boston University School of Medicine and College of Engineering, led by Dr. Avrum Spira, uncovered these genes by using high-density microarrays to compare gene expression among 34 current smokers, 18 past smokers, and 23 never smokers. The majority of these 97 genes encode proteins involved in stress response; the cell raises or lowers the expression of these genes to help protect itself against the toxic effects of cigarette smoke. Not surprisingly, several potential tumor suppressor genes and oncogenes also show altered expression in smokers.

There was a small subset of three current smokers with a different expression profile; many of their stress genes did not alter expression when exposed to cigarette smoke. Since they showed a deficient stress response, these smokers potentially have an increased risk of smoking-related damage. This finding might indicate that some people have a predisposition to cancer and other ill-effects of smoking.

Dairy and Colorectal Cancer

Dairy consumption may be inversely associated with development of colorectal cancer. A study in the July 7 Journal of the National Cancer Institute reported that both milk and calcium intake could reduce the risk of colorectal cancer, while other dairy products such as yogurt and cheese were not found to have a significant association. Researchers in North America and Europe participated in this study, which was led by Dr. Eunyoung Cho of Harvard Medical School. Ten cohort studies were pooled for analysis having a total of 534,536 subjects and a follow-up range between 6 and 16 years.

Colorectal cancer is considered a highly treatable condition and is cured in about 45 percent of patients who undergo treatment. Surgery is the primary therapy for the disease. Lowering cancer risk reduces undue pain and suffering and decreases health care costs associated with surgery and other treatments.

In this study, milk was found to be the only dairy product of statistical significance to lower colorectal cancer risk. The relationship between milk and colorectal cancer was highly consistent across the 10 studies. The authors also studied calcium intake and found it to have an inverse association with colorectal cancer as well, but with a threshold effect observed within the data; little further benefit was seen in risk reduction for colorectal cancer when individuals ingested more than 1,000 milligrams of calcium per day.

Endothelial Cells May Provide Insight into Angiogenesis

The cells lining B-cell lymphoma blood vessels take on genetic characteristics of the tumors themselves, according to a study published in the July 15 New England Journal of Medicine. Dr. Berthold Streubel and colleagues at the Medical University of Vienna show that although these cells were commonly believed to be genetically stable and normal, the reality is much more complicated.

In order to secure an oxygen supply, tumor cells must induce nearby blood vessels to grow - a process called angiogenesis. The researchers studied tissue from 27 B-cell lymphomas with known chromosomal abnormalities. In all the lymphomas examined, varying proportions of blood vessel cells shared the tumor cells' chromosomal aberrations.

Researchers conclude there is a genetic relationship between these cells, the nature of which remains unclear. They propose several possible explanations: 1) the tumor and endothelial cells may share a common precursor, 2) some endothelial cells may share the lymphoma's genetic abnormalities because they arise from a cell already committed to a lymphoid lineage, 3) these endothelial cells could be the result of cell fusion, or 4) they may become polyploid by engulfing apoptotic bodies from tumor cells.

In an accompanying commentary, Drs. Isaiah Fidler and Lee Ellis of the University of Texas M.D. Anderson Cancer Center in Houston assert that "the important message from this insightful study is that tumor microvasculature is much more complex and unpredictable than it was initially perceived to be." Uncovering and recognizing these complexities will help researchers develop better anti-angiogenesis treatments.

Improving Detection for Ovarian Cancer

Drs. Thomas Conrads and Tim Veenstra of the Laboratory of Proteomics and Analytical Technologies at NCI-Frederick (operated by SAIC-Frederick, Inc.) in collaboration with NCI researchers published a study in the June 2 issue of Endocrine-Related Cancer discussing how mass spectrometry (MS) combined with new technology might improve detection for ovarian cancer. Other research hypothesized that MS could be used as a tool in the detection of breast, ovarian, and prostate cancers; however, instead of attempting to identify a single biomarker, researchers instead used patterns of mass spectral features comprising peptide or other ions as the diagnostic tool itself in determining whether high- or low-resolution spectra have more sensitivity and/or specificity.

In the past, ovarian cancer detection has relied upon the elevation of cancer antigen 125 (CA 125), the ovarian cancer biomarker detected by the monoclonal antibody OC 125. Although levels of CA 125 are reportedly higher in 80 percent of patients with advanced ovarian cancer, elevated levels are detected in only approximately 50 to 60 percent of women with stage one disease.

Researchers analyzed 248 patient serum samples obtained from the National Ovarian Cancer Early Detection Program and the gynecologic oncology clinic at Northwestern University. These samples were examined using both high- and low-resolution mass spectrometers. The group of sera analyzed was divided into three data sets to determine the sensitivity and specificity of the samples. For all sets, both sensitivity and specificity results were higher for the high-resolution MS than for low-resolution MS. Single biomarkers lack sensitivity and specificity when applied to large, heterogeneous populations; the new technology of biomarker pattern analysis may help overcome this limitation to improve patient survival rates and treatment options.