© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 12, 887,
June 20, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Malignant gliomas are brain tumors characterized by their aggressiveness and resistance to standard therapies; long-term survival after diagnosis with this tumor is rare. On the basis of specific signaling pathways that are commonly activated in gliomas, investigators have attempted to use reovirus, a tumor-killing virus that exploits these pathways, to treat gliomas in experimental systems. Wilcox et al. (p. 903) tested the activity of reovirus against a variety of human malignant glioma cell lines and human tumors grown in mice and found that the virus killed most of the cell lines tested and caused substantially improved survival of glioma-bearing mice. Primary tumors removed from humans were also susceptible to killing by reovirus. The authors suggest that, if potential short- and long-term safety issues of reovirus treatment can be favorably addressed, this virus could be a candidate for clinical trials in humans.
In an accompanying editorial, Gromeier (p. 889) discusses the need to address key issues early in the development of viral antitumor therapies. These issues include the affinity of a virus for a target tissue; its virulence—that is, how quickly it spreads; and the potential for disease associated with viral infection.
EGF Receptor, Gene Therapy, and Radiosensitivity
Ionizing radiation is effective in treating some cancers. However, in other cancers, such as some breast cancers, ionizing radiation activates the epidermal growth factor receptor (EGFR), which in turn protects the cancer cell from radiation-induced cell damage. To bypass this protective mechanism, Lammering et al. (p. 921) employed a dominant-negative mutant EGFR that, when introduced into breast cancer cells in vitro, blocks the activity of the endogenous EGFR. The authors cloned the mutant EGFR into an adenoviral vector to determine if they could target the EGFR in vivo in xenograft tumors growing in nude mice. The authors found that the adenoviral vector containing the mutant EGFR could be efficiently introduced in vivo and that, when expressed, the mutant EGFR increased the sensitivity of the tumor to ionizing radiation. The authors suggest that targeting EGFR function by the mutant EGFR might be an effective gene therapeutic approach to increase sensitivity to ionizing radiation.
In an editorial (p. 890), Ethier and Lawrence discuss why EGFR is an important therapeutic target in cancer treatment and the issues that should be considered to maximize the probability that the combination of radiation with EGFR intervention strategies will be effectively translated to a clinical setting.
Prognostic Markers for Lymph Node-Negative Breast Cancer
Traditional tumor characteristics and clinical factors fail to identify high-risk patients who will require adjuvant chemotherapy. Jänicke et al. (p. 913) present the first interim analysis of a multicenter, randomized trial investigating whether urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) could identify such high-risk patients. By measuring uPA and PAI-1 antigen levels in primary tumors of women with lymph node-negative breast cancer, they classified about half of the patients as low risk, for whom adjuvant chemotherapy may be avoided, and about half as high risk, who appear to benefit from adjuvant chemotherapy. The authors recommend larger scale testing of tumor levels of uPA and PAI-1 in patients with primary lymph node-negative breast cancer.
"We confirm the strong and independent prognostic importance of tumor levels of uPA and PAI-1 for patients with lymph node-negative breast cancer."
—Jänicke et al.
Bone Mass and Breast Cancer Risk in Older Women
While older women with low bone mass have a decreased incidence of breast cancer, it is not known whether this association is confined to mammographically detected early-stage, slow-growing tumors. Zmuda et al. (p. 930) measured bone mineral density (BMD) at the wrist, forearm, and heel of white women aged 65 years and older who were enrolled in the Study of Osteoporotic Fractures. After a mean of 6.5 years of follow-up, the authors found that the women with the highest BMD at all three skeletal sites had a 2.7 times greater risk of breast cancer than women with the lowest BMD at all three sites. Moreover, this risk was greater for more advanced tumors than it was for early-stage tumors. The authors conclude that high bone mass is a powerful predictor of breast cancer, especially more advanced cancer, among older women.
Helicobacter pylori and Risk of Pancreatic Cancer
Pancreatic cancer is highly lethal, and its causes are poorly understood. Because the ulcer-related bacterium Helicobacter pylori sometimes causes stomach cancer, and because pancreatic cancer is associated with a history of surgery for benign gastric conditions including ulcers, Stolzenberg-Solomon et al. (p. 937) investigated whether infection with this bacterium might also play a role in pancreatic cancer. Using a case–control study design nested within a prospective study of male smokers in Finland, the investigators measured antibodies to H. pylori and compared H. pylori carrier status in subjects with and without pancreatic cancer. Although the seroprevalence of H. pylori was high in both case and control subjects, individuals carrying H. pylori appeared to be at higher risk of pancreatic cancer and certain strains were associated with an approximately twofold risk increase. The authors recommend that additional studies are warranted to evaluate this relationship and to improve understanding of the mechanism.
Physical Activity and Ovarian Cancer
Studies testing the hypothesis that physical activity reduces the risk of ovarian cancer have produced inconsistent results. Bertone et al. (p. 942) used data from the prospective Nurses’ Health Study cohort to further test the relationship. During a 16-year follow-up of 92,825 women, 377 cases of epithelial ovarian cancer were confirmed. No statistically significant risk reduction was found in women who exercised more than 7 hours per week compared with women who exercised 1 hour or less per week. They conclude that, overall, their results did not suggest an inverse association between recreational physical activity and ovarian cancer.
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