© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 1, 1,
January 6, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Breast cancers can become resistant to treatment with the drug tamoxifen. Arteaga et al. (p. 46) have performed studies to uncover mechanisms that may play a role in this resistance. By use of a tamoxifen-resistant human breast cancer cell line, LCC2, and a related tamoxifen-sensitive line, LCC1, they showed that large amounts of transforming growth factor-ß2 were secreted by the resistant line but not by the sensitive line. They also showed that the growth of LCC2 tumors in nude mice could be inhibited by treatment with tamoxifen and neutralizing antibodies against transforming growth factor-ß. Similar treatment did not inhibit LCC2 tumor growth in beige/nude mice, which are deficient in natural killer cell function. These data suggest that the antitumor effects of tamoxifen may be mediated, in part, by natural killer cell function and that, by abrogating this mechanism, transforming growth factor-ß2 may contribute to tamoxifen resistance.
Telomerase: Cellular Immortality and Its Reversal
Telomerase, the enzyme responsible for maintaining the length of telomeres (the ends of chromosomes) during DNA replication, is repressed in normal cells, leading to a progressive shortening of telomeres and the arrest of cell growth. In cancerous cells, the telomerase is active, facilitating telomere maintenance and allowing continuous cell growth. Cuthbert et al. (p. 37) investigated whether specific chromosomal DNA sequences are responsible for repressing telomerase in normal cells and are either defective or absent in cancer cells. They found that chromosome 3 (in contrast to chromosome 8, 12, or 20) of normal human cells, when experimentally introduced into cancer cells, can repress telomerase activity and induce growth arrest. This shows that specific telomerase repressor sequences present on normal chromosome 3 are not functional in cancer cells. In addition, the authors have identified, by detailed gene mapping, two regions on the short arm of chromosome 3 where telomerase regulator genes may be located.
In an editorial, Shay (p. 4) notes the importance of identifying genes in the telomerase repression pathway and discusses the prospects of treating cancer by inhibiting telomerase. After treatment with conventional regimens, anti-telomerase agents may be used to limit the proliferative capacity of surviving cancer cells and prevent recurrence. He suggests that use of telomerase inhibitors along with other cancer therapeutic agents may more effectively achieve complete cancer remissions.
Ferrets, ß-Carotene, and Tobacco Smoke
Recent intervention studies have demonstrated an increase in the risk of lung cancer among smokers taking high doses of ß-carotene—an unexpected result given epidemiologic studies that show a lower risk of cancer, especially lung cancer, among individuals who eat more fruits and vegetables, which are rich in ß-carotene. Wang et al. (p. 60) have used ferrets, which absorb and metabolize ß-carotene similarly to humans, to determine the molecular effects of ß-carotene in the presence and absence of tobacco smoke. The authors report that expression of retinoic acid receptor ß is suppressed and that activator protein-1 is overexpressed in the lung tissue of animals receiving high doses of ß-carotene and exposed to tobacco smoke. These molecular alterations could lead to diminished retinoid signaling and accelerated cell proliferation, possibly enhancing lung tumor formation.
In an editorial, Lotan (p. 7) discusses the results of Wang et al., including their explanation for the enhancing effect of ß-carotene supplementation on lung cancer in smokers. He points out the ways in which the response to ferrets exposed to smoke, the animal model used, is similar to and different from the response of humans exposed to smoke, especially with regard to squamous metaplasia. He suggests caution when extrapolating the findings from the ferret to human lung carcinogenesis.
Vinorelbine, Quality of Life, and Advanced Non-Small-Cell Lung Cancer
There are few chemotherapeutic options available for patients with advanced non-small-cell lung cancer, especially for those, such as elderly patients, who may not to be able to tolerate potential toxic effects. Vinorelbine is a drug that is well tolerated by elderly patients with this form of cancer. The Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) Group (p. 66) reports that vinorelbine treatment improves the survival of elderly patients with advanced disease and possibly improves their overall quality of life.
Breast Cancer and Marital Stability
The belief that husbands desert their wives who have breast cancer is not uncommon but has been based to a large extent on anecdotal evidence found in popular women's magazines. In a study of women from Quebec City and its surrounding regions, Dorval et al. (p. 54) have compared the frequency of marital breakdown among women who had breast cancer with that among control women. They found that marital breakdown was never higher in women with breast cancer than in control women, and they conclude that breast cancer does not appear to be associated with marital breakdown among Quebec women.
Predicting Sarcoma Aggressiveness
Several types of sarcomas—cancers primarily of connective tissue origin—are characterized by aberrations of human chromosome 9. Orlow et al. (p. 73) investigated whether there was an association between alterations (deletions and rearrangements) in certain genes related to the control of cell growth that map to chromosome 9 and the aggressiveness of the sarcoma. In a study of sarcomas from 46 patients, the researchers characterized the status of the neighboring INK4A and INK4B genes in cells from the patient's sarcoma, as well as the status of known tumor suppressor genes and oncogenes. They were particularly interested in changes in INK4A, a gene unusual in that it encodes two distinct proteins, p16 and p19ARF (for alternate reading frame). Orlow et al. found a statistically significant association between alterations in INK4A and INK4B and poor survival of the patient. The researchers suggest that these gene alterations may provide clues to the prognosis and proper treatment of patients with sarcomas.
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