© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 18, 1525,
September 15, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
In 1989, a model was developed by M. H. Gail and colleagues for estimating the risk of breast cancer in women participating in a program of annual mammographic screening. In 1992, statisticians of the National Surgical Adjuvant Breast and Bowel Project modified this model to project the risk of developing only invasive breast cancer. Costantino et al. (p. 1541) have assessed the validity of both these models by employing data from a subset of annually screened white women who were assigned to receive placebo in the Breast Cancer Prevention Trial. The original model, but not the modified one, underestimated the absolute risk of breast cancer in women over the age of 59 years in relation to their predicted 5-year risk. Both models exhibited a tendency to overestimate risk for women classified in the higher quintiles of predicted risk and to underestimate risk for those in the lower quintiles.
Potential Treatment for Cisplatin-Resistant Ovarian Cancer
The accepted first-line treatment of advanced ovarian cancer is surgical reduction followed by chemotherapy with a regimen that usually includes a platinum-containing compound (e.g., cisplatin). Even though the disease may respond to this treatment, the recurrence of drug-resistant disease is common. Thus, new strategies are needed for the management of advanced ovarian cancer. In a series of laboratory experiments, Duska et al. (p. 1557) have explored the use of photoimmunotherapy—a technique employing laser beams to activate compounds attached to antibodies directed against tumor cells—in combination with cisplatin chemotherapy. The researchers found that the combination treatment was substantially more toxic to tumor cells than either treatment alone. In cisplatin-sensitive cells, the effects of the two treatments appeared additive; in cisplatin-resistant cells, however, greater cell death occurred than was expected from the individual treatments.
". . . [T]here is a clear need for the development of new strategies for the management of advanced epithelial ovarian cancer."—Duska et al.
Another Tumor Suppressor on Chromosome 3?
A variety of human tumors have been found to be associated with changes in chromosome region 3p14. To investigate genes in this region that might be involved in kidney cancer, Jühlicher et al. (p. 1563) introduced members of a library of yeast artificial chromosomes (YACs) carrying human 3p14 sequences into cells from RCC-1, a human kidney cancer cell line. The researchers found that introduction of a particular YAC, carrying sequences from chromosomal region 3p14.2, was able to suppress tumor formation when the YAC-carrying cells were injected into immunodeficient nude mice but not when the cells carried an unrelated YAC or vector sequences alone. The investigators think that the data provide strong evidence for a novel tumor suppressor locus close to the previously identified FHIT gene.
"Overall, these data suggest that several genes within [human chromosome region] 3p14 and neighboring bands may be involved in the control of senescence, telomerase activity, and tumorigenesis."—Jühlicher et al.
Gene Transfer and Glioma Progression
Abounader et al. (p. 1548) have transfected human glioblastoma cells with gene constructs that contain U1 small nuclear RNA, a hammerhead ribozyme, and antisense sequences to target specific sites on messenger RNAs encoding scatter factor/hepatocyte growth factor (SF/HGF) and its receptor, c-met. Expression of these proteins is often associated with malignant progression of human tumors, including gliomas. Following treatment with these constructs, the investigators observed reduced expression of the SF/HGF and c-met genes, and they observed an inhibition of SF/HGF-mediated signal transduction (i.e., SF/HGF-dependent induction of the c-fos and c-jun genes). They also noted an inhibition of anchorage-independent colony formation (an in vitro correlate of solid tumor malignancy) and inhibition of intracranial tumor formation and growth in immunodeficient mice. The authors conclude that targeting the SF/HGF-c-met signaling pathway may be an important approach in controlling tumorigenicity and tumor progression.
"Practical approaches that [can] overcome obstacles of delivering genetic [materials] . . . across the blood-brain barrier to invasive neoplasms will be needed . . . before . . . similar [gene] therapeutic strategies can be extrapolated to man."—Abounader et al.
p16 Mutations in Primary Tumors
Point mutations in the gene for p16 are found in many types of cancers. Yarbrough et al. (p. 1569) investigated the functional activities of a wide range of naturally occurring p16 mutant proteins. They report that nine of the 16 mutants analyzed had functional defects in cyclin-dependent kinase binding, kinase inhibition, and/or cell cycle arrest. All nine mutations causing functional defects mapped to the central portion of the p16 protein, suggesting that mutations in ankyrin repeats II and III are more critical to p16 function.
Chromosome 8 and Prostate Cancer
Genetic changes in chromosome 8 are commonly observed in prostate cancers. Sato et al. (p. 1574) have examined alterations at two locations (8p21-22 and 8q24) to determine whether they are associated with a poor prognosis. The authors report that genetic alterations of chromosome 8 appear to accumulate in parallel with the progression of prostate carcinomas.
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