© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 22, 1671,
November 21, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Although estrogen can promote the growth of estrogen receptor-positive breast cancers, high doses of estrogen can have the paradoxical effect of promoting tumor regression in postmenopausal women. To investigate the mechanism of tumor regression, Song et al. (p. 1714) made use of LTED, E8CASS, and BSK3 cells, which are MCF-7 breast cancer cells grown for many months in the absence of estrogen. LTED cells treated with high doses of estradiol showed decreased cell growth and increased apoptosis. Identically treated MCF-7 cells, by contrast, grew at increased rates and showed reduced apoptosis. Several lines of evidence indicate that the induction of apoptosis in LTED and E8CASS cells by estradiol may be mediated by the Fas/FasL signaling pathway. The authors note that the phenotype of estrogen-deprived MCF-7 cells suggests that high-dose estrogen treatment may have clinical relevance in postmenopausal women with breast cancer.
In an editorial, Soto and Sonnenschein (p. 1673) discuss the larger issue of how sex steroid hormones can have both inhibitory and stimulatory effects on their target organs. They note that a better understanding of the conditions under which these hormones promote apoptosis could ultimately improve the prognosis of both breast and prostate cancer patients.
Trends in U.S. Cancer Screening
Much of the public health benefit of cancer screening depends on its utilization. Breen and colleagues (p. 1704) analyzed three years of data (1987, 1992, and 1998) from the National Health Interview Survey to examine levels and trends in the use of several cancer screening tests—Pap smears, mammography, fecal occult blood tests, endoscopy, and digital rectal examination—in the United States. They observed that use of all tests increased over the time period under study and that colorectal cancer screening (both endoscopy and fecal occult blood test) continued to lag behind mammography screening for breast cancer. They also found that screening at recommended time intervals was lower across all tests for people with lower education, income, and access to health insurance or a regular source of health care.
In an editorial, Frame (p. 1676) explores the consequence of increased screening as it pertains to the primary physician–patient relationship. He points out that awareness has increased and more people from different ethnicities are being screened, but he notes that there is still room for improvement on the part of all people within the health care profession.
Interleukin 15 and Epstein-Barr Virus-Infected Lymphocytes
Interleukin 15 (IL-15) activates cytotoxic lymphocytes and drives the expansion of memory T cells. Epstein-Barr virus (EBV) is a highly potent lymphocyte-transforming herpesvirus associated with several human tumors. Sharif-Askari et al. (p. 1724) investigated the role of IL-15 in controlling EBV-transformed/immortalized lymphocytes in culture. They infected peripheral blood mononuclear cells (PBMCs) with EBV and cultured them with IL-15 for 3 to 4 weeks. The presence of IL-15 resulted in the complete elimination of EBV-transformed cells. The investigators then depleted EBV-infected cultured PBMCs of specific cell populations, and they found that the anti-EBV effect was contributed initially by activated natural killer (NK) cells and subsequently by cytolytic NK-T cells. The authors conclude that, if these in vitro findings reflect the in vivo mechanisms, IL-15 might be considered for cytokine-based immunotherapy in patients with EBV-associated lymphoproliferative disorders/malignancies.
Incidence of Metachronous Testicular Cancer
Men who have had testicular cancer have a relatively high risk of developing a subsequent contralateral testicular cancer. Whether the same is true for men who have had an extragondal germ cell tumor (EGCT) is unclear. In an international retrospective study of 635 EGCT patients, Hartmann et al. (p. 1733) determined the incidence, cumulative risk, and specific risk factors for metachronous testicular cancer. The authors found that 16 of 635 patients developed metachronous testicular cancer despite the use of chemotherapy for the EGCT and that the risk of developing the disease was statistically significantly increased in EGCT patients, particularly in those who had retroperitoneal or nonseminatous EGCT. The authors also found that patients with primary mediastinal EGCT are at an increased risk of metachronous testicular cancer.
Androgen-Independent Prostate Cancer and Dexamethasone
Dexamethasone, a synthetic glucocorticoid, has clinical benefit for patients with hormone-refractory prostate cancer. Nishimura et al. (p. 1739) have identified a potential mechanism to explain its effects in such patients. The authors show that only prostate cancer cell lines that express the glucocorticoid receptor are growth inhibited by dexamethasone and that dexamethasone inhibits the movement to the nucleus of the transcription factor NF-
B. One consequence of disrupting NF-B was that levels of the cytokine interleukin 6 (IL-6), which is thought to stimulate growth of hormone-refractory prostate cancer cells, were decreased in dexamethasone-treated cells. The authors also show that a low treatment dose of dexamethasone inhibited the growth of prostate cancer xenografts without affecting glucocorticoid receptor levels. The authors conclude that dexamethasone inhibited the growth of glucocorticoid receptor-positive prostate cancers, possibly through the disruption of the NF-B–IL-6 pathway.
Measuring GSTP1 Methylation in Prostate Cancer
Reliable methods to detect early-stage prostate cancer are needed because treatment of advanced-stage disease has only limited success. Methylation of regulatory sequences near the 
class glutathione S-transferase gene (GSTP1) is the most common epigenetic alteration associated with prostate cancer. Jerónimo et al. (p. 1747) measured GSTP1 methylation in histopathologically distinct prostate tissue samples and in sextant prostate biopsy specimens from patients with elevated serum levels of prostate-specific antigen. They found that benign hyperplastic prostatic tissue, intraepithelial neoplasia, and adenocarcinoma had statistically significantly different levels of GSTP1 methylation. Moreover, prospectively collected sextant biopsy specimens from patients with adenocarcinoma had higher levels of GSTP1 methylation than those from patients with no evidence of adenocarcinoma. The authors conclude that quantitation of GSTP1 methylation could improve prostate cancer detection by allowing the accurate discrimination between normal hyperplastic tissue and prostatic carcinoma.
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