News Release

Other highlights of the February 19 JNCI

Peer-Reviewed Publication

Journal of the National Cancer Institute

DNA repair capacity associated with cutaneous malignant melanoma
Reduced DNA repair capacity is an independent risk factor for cutaneous malignant melanoma and may contribute to susceptibility to sunlight-induced cutaneous malignant melanoma among the general population, according to a study in the February 19 issue of the Journal of the National Cancer Institute.

Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of cutaneous malignant melanoma, which suggests that DNA repair capacity may also play a role in sunlight-induced melanoma within the general population. Qingyi Wei, M.D., Ph.D., and colleagues at the University of Texas M. D. Anderson Cancer Center, Houston, conducted a study of DNA repair capacity and melanoma among 312 patients with cutaneous malignant melanoma and 324 cancer-free control subjects.

They found that case patients had a 19% lower mean DNA repair capacity than control subjects, and that a DNA repair capacity at or below the median value of that in control subjects was associated with increased risk for melanoma. Patients with tumors on sun-exposed skin had a lower DNA repair capacity than patients with tumors on unexposed skin.

Contact: Laura Sussman, M. D. Anderson Cancer Center, 713-792-0655, lsussman@mdanderson.org

Natural compound shows promise as lung cancer chemoprevention agent
A natural compound called deguelin may have potential as both a chemopreventive agent and a therapeutic agent against lung cancer, according to a study in the February 19 issue of the Journal of the National Cancer Institute.

Deguelin, present in several plant species, including Mundulea sericea, is in a class of compounds called rotenoids, which have been found to exhibit chemopreventive activity. Kyung-Hee Chun and Ho-Young Lee, Ph.D., of the M. D. Anderson Cancer Center, and their colleagues evaluated the chemopreventive effects of deguelin in normal, premalignant, and malignant human bronchial epithelial cells.

Deguelin inhibited the growth of and induced apoptosis of premalignant and malignant human bronchial epithelial cells by affecting the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. However, deguelin had minimal effects on the normal bronchial cells. The authors conclude that the ability of deguelin to inhibit PI3K/Akt-mediated signaling pathways may contribute to the potency and specificity of this drug and that, because both premalignant and malignant bronchial cells are more sensitive to deguelin than normal bronchial cells, deguelin may have potential as both a chemopreventive agent and a therapeutic agent against lung cancer.

Contact: Laura Sussman, M. D. Anderson Cancer Center, 713-792-0655, lsussman@mdanderson.org

Also in the February 19 JNCI:

  • OK-432 immunotherapy and Toll-like receptor 4: The streptococcal agent OK-432 has been used for immunotherapy of head and neck cancer, but its mechanism of action is unknown. Because the Toll-like receptor 4 (TLR4)/MD-2 complex is important in enabling the mammalian immune system to recognize bacterial components, Masato Okamoto and Mitsunobu Sato, D.D.S., Ph.D., of the Tokushima University School of Dentistry, investigated whether expression of the TLR4 and MD-2 genes is associated with OK-432-induced anticancer immunity. Expression of TLR4 and MD-2 genes was associated with the in vivo induction of interferon-gamma in 19 patients administered OK-432. By using mice that were deficient in TLR4, they also found that intraperitoneal administration of OK-432 resulted in reduced tumor volume and increased interferon-gamma in sera from wild-type mice but not in sera from TLR4-deficient mice. The authors conclude that TLR4 and MD-2 may mediate OK-432-induced anticancer immunity.

  • DNA methylation and pancreatic cancer cell invasiveness: DNA methylation plays an important role in the regulation of various genes that determine the behavior of cancer cells. To investigate a possible association between DNA methylation and the invasive phenotype of pancreatic adenocarcinoma, Norihiro Sato, Michael Goggins, M.D., and colleagues from the Johns Hopkins Medical Institutions studied the role of methylation in the transcriptional regulation of several matrix metalloproteinases (MMPs) and the effect of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5Aza-dC) on the invasive behavior of pancreatic cancer cells. They found a statistically significant increase in invasive potential in four of five pancreatic cancer cell lines after treatment with 5Aza-dC. The addition of an MMP inhibitor blocked the 5Aza-dC-induced increase in the number of invading cells. The authors conclude that DNA methylation influences the expression of MMP genes, and use of methylation inhibitors may stimulate the invasion of pancreatic cancer by reactivating invasion-promoting genes.

  • Quality-of-life measurement and breast cancer: Measurement of health-related quality of life (HRQOL) in clinical trials in breast cancer has become common. In a review, Pamela J. Goodwin, M.D., of Mount Sinai Hospital, Toronto, and colleagues identified 66 randomized clinical trials from 1975 through 2001 that included HRQOL measurements; 46 evaluated biomedical and 20 evaluated psychosocial interventions. The authors found that the contribution of HRQOL measurement in biomedical intervention trials depended on the clinical setting, with HRQOL measurement influencing clinical decisions in the primary management setting and in the symptom control setting, while providing little information in the adjuvant and metastatic settings. In the psychosocial trials, HRQOL measurements often provided the only outcome information. The authors recommend caution in initiating new HRQOL studies unless treatment equivalency is expected or unless the HRQOL question targets specific issues that can only be addressed by patient self-report.

###

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.