© Oxford University Press 2006.
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-Actin and Resistance to Microtubule Targeting Drugs
Acute lymphoblastic leukemia (ALL) cells resistant to microtubule-disrupting drugs express altered versions of actin. Verrills et al. (p. 1363) examined whether these altered proteins are involved in resistance to antimicrotubule agents. They found that ALL cells resistant to antimicrotubule agents expressed mutant -actins but no wild-type -actin. Mouse cells expressing mutant -actin proteins were more resistant to antimicrotubule agents than cells transfected with empty plasmid, as were human neuroblastoma cells transfected with -actin siRNA compared with mock-transfected cells. Expression of -actin was lower in ALL samples collected at relapse than at diagnosis. The authors conclude that loss of wild-type -actin may mediate resistance to antimicrotubule drugs.
In an editorial, Fojo (p. 1345) discusses these findings in the context of what is known about the actin and microtubule cytoskeletons and their interactions. He notes that independent confirmation of the findings is required.
Antibiotic Treatment of Ocular Adnexal Lymphoma
Ocular adnexal lymphoma (OAL) originates in the eye or surrounding tissues. Although rarely lethal, it can substantially compromise quality of life. Recent findings indicate an association between infection with the bacterium Chlamydia psittaci and the development of OAL. Ferreri et al. (p. 1375) treated 27 OAL patients with a 3-week course of the antibiotic doxycycline. Tumors regressed completely in six patients, and in seven additional patients tumors shrunk by more than 50%. Noting that both patients with and without evidence of C. psittaci infection responded, the authors conclude that doxycycline is active against OAL and that more sensitive methods for bacteria detection in OAL patients may be needed.
In an editorial, Zucca and Bertoni (p. 1348) discuss OAL and other lymphomas that may be caused by infectious micoorganisms and comment on the surprising finding that even patients who did not test positive for infection responded to doxycycline.
Consortia Study of Genetic Associations in Breast Cancer
Some changes in cancer susceptibility genes confer large increases in risk, but the effects of most are likely modest. Genetic association studies rarely have sufficient power to detect low to moderate changes in risk, and many initial reports turn out to be false. Collaborating groups can produce the large sample sizes necessary for more powerful association studies. The Breast Cancer Association Consortium (p. 1382) report combined analyses of 16 single-nucleotide polymorphisms (SNPs) for their associations with breast cancer. Data from 12,000–32,000 subjects were analyzed for each SNP. Five SNPs showed borderline statistically significant associations. The other 11 SNPs were not associated with breast cancer, even though nine had shown an association in previous, smaller studies.
In an editorial (p. 1350), Ioannidis agrees that conclusive genetic evidence will require large sample sizes and suggests that the consortium approach is preferable to traditional meta-analyses because it avoids publication biases. He notes that consortia investigators should perform genotyping prospectively and use high-quality data to minimize errors.
Menopausal Hormone Therapy and Ovarian Cancer Risk
The relationship between ovarian cancer risk and the use of menopausal hormone therapy is unclear. Lacey et al. (p. 1397) analyzed data from more than 97,000 women aged 50–71 who participated in the National Institutes of Health–AARP Diet and Health Study Cohort. Compared with no hormone therapy use, use of unopposed estrogen for fewer than 10 years was not associated with increased ovarian cancer risk, but use for 10 or more years was (56 vs. 72 ovarian cancers per 100,000 person-years). Among women who had not had a hysterectomy, use of combined estrogen and progestin therapy for 5 or more years was also associated with an increased risk of ovarian cancer (49 vs. 108 per 100,000 person-years for sequential regimens, 49 vs. 66 per 100,000 person-years for continuous regimens). The authors conclude that long-term use of unopposed estrogen and of estrogen plus progestin is associated with increased ovarian cancer risk in this population.
Persistent Risk of Suicide After Breast Cancer Diagnosis
To investigate long-term suicide risk among breast cancer survivors, Schairer et al. (p. 1416) quantified suicides among more than 700,000 1-year breast cancer survivors using data from 16 population-based registries in the United States and Scandinavia. Through 2002, 836 survivors committed suicide, including 245 in the United States. The suicide risk was elevated for at least 25 years after diagnosis and was highest among black women. The risk rose with increasing breast cancer stage and remained elevated among patients diagnosed between 1990 and 2001. The cumulative probability of suicide 30 years after diagnosis was 0.20%. Although the increased suicide risk was small, the authors write that long-term follow-up for breast cancer survivors should include psychosocial resources.
Hormones and Premenopausal Breast Cancer Risk
In premenopausal women, the relationship between endogenous sex steroid hormone levels and the risk of breast cancer is unclear, in part because measuring hormone levels that vary cyclically is complex. Eliassen et al. (p. 1406) performed a prospective nested case–control study to evaluate associations between breast cancer risk and plasma sex hormone levels among 18,521 women who provided blood samples during the early follicular and midluteal phases of their menstrual cycles. Higher total and free estradiol levels in the early follicular phase and total and free testosterone levels in both phases were associated with increased breast cancer risk. The authors write that circulating estrogen and androgen levels may be important in the etiology of premenopausal breast cancer.
Predicting Recurrence of Prostate Cancer with AZGP1
Many prostate cancer patients have their prostate gland surgically removed. It is important to identify those who are at risk for recurrence and need additional therapy. Henshall et al. (p. 1420) examined levels of the protein AZGP1 in prostate tissue from 228 patients who had their prostates removed. Those whose tissue contained low levels of AZGP1 were more likely to both experience a recurrence and die from the disease than patients with high AZGP1 levels. The authors suggest that AZGP1 testing may identify patients who require further therapy after prostate removal.
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