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Sequential Topotecan in Advanced Ovarian CancerThe combination of carboplatin and paclitaxel is the standard of care for ovarian cancer treatment, yet rates of recurrence and death remain high. In a randomized phase III trial of 1308 patients, Pfisterer et al. (p. 1036) examined whether sequential administration of topotecan would improve overall survival, overall response, and progression-free survival in patients receiving carboplatin–paclitaxel as first-line treatment for advanced epithelial ovarian cancer. It did not. Moreover, sequential topotecan caused more hematologic toxic effects (requiring more supportive care) and infections. The authors conclude that carboplatin–paclitaxel alone should remain the standard of care for patients with advanced ovarian cancer.
In an editorial, McGuire (p. 1024) reviews other negative trials in advanced ovarian cancer treatment that have used these drugs in triplet combinations or in sequential therapy. He suggests that the way forward is through trials of targeted therapies that have shown promise in other solid tumors.
Race-related Distribution and Persistence of HPV 16 and 18
Several studies have described differences in the geographic distribution of variants of human papillomavirus (HPV) types. Xi et al. (p. 1045) investigated whether the distribution and persistence of variants of HPV types 16 and 18 were related to the racial composition of a population living in one geographic region. They found that African HPV variants were predominant in HPV-infected African American women, and European variants were predominant in HPV-infected white women. The likelihood of remaining HPV positive followed the same pattern. The authors conclude that variants of HPV 16 and 18 appear to persist longer in women whose race indicates that their ancestors and the variants once shared a geographic area.
In an editorial, Burk and DeSalle (p. 1026) note that the cancer-causing HPV types—HPV16 and HPV18—appear to be interacting with some unknown human characteristics associated with race. The problem is sorting out what these factors are and how the relationships among virus variation, host variation, and persistence lead to cancer.
Inconsistent Hospice Use Among Cancer Patients
Hospice care can improve the management of symptoms and quality of life for terminally ill cancer patients, but rates of hospice enrollment vary substantially. To better understand how local practice patterns and individual physicians contribute to this variability, Keating et al. (p. 1053) examined data from 3805 patients who were diagnosed with and died from lung, colorectal, breast, or prostate cancer while enrolled in a regional health plan. Hospice enrollment varied substantially among the 11 health centers studied but less among the 675 treating physicians. Most patient sociodemographic characteristics were not contributing factors to hospice enrollment. The authors conclude that efforts to understand how patients, physicians, and hospices interact are important to ensure equal access to hospice care for all terminally ill cancer patients.
SOX 18 Transcription Factor and Tumor Angiogenesis
The transcription factor SOX18 is expressed in endothelial cells and is involved in maintaining blood vessel integrity. To determine the role of SOX18 in tumor blood vessels, Young et al. (p. 1060) analyzed angiogenesis and growth of melanoma allograft tumors in wild-type mice, SOX18 null mice, and mice that express a dominant-negative form of SOX18. They also examined capillary formation in human umbilical vein endothelial cells expressing wild-type or dominant-negative SOX18. The authors found that allograft tumors in SOX18-null mice and mice expressing the dominant-negative SOX18 grew more slowly than allograft tumors in wild-type mice. Expression of the dominant-negative SOX18 in endothelial cells disrupted cell structure and impaired capillary formation. The authors suggest that SOX18 may be a useful target for antiangiogenesis therapy.
Anti-Leukemia Activity of Shepherdin Molecule
Shepherdin inhibits the interaction between heat shock protein 90 (Hsp90), which is involved in signaling pathways for cell proliferation and survival, and survivin, which is a regulator of cell proliferation and viability. Gyurkocza et al. (p. 1068) investigated shepherdin as a potential agent for treating acute myeloid leukemia (AML). Shepherdin rapidly killed AML cells but did not affect normal cells. It also abolished growth of AML xenograft tumors in mice without producing systematic toxic effects. Shepherdin disrupted mitochondrial function within 2 minutes of treatment and eliminated the expression of Hsp90 client signaling proteins. The authors conclude that shepherdin or its derivatives should be developed further as a possible treatment for AML.
Processed Meat Intake and Risk for Stomach Cancer
To summarize the current data available on processed meat intake and stomach cancer risk, Larsson et al. (p. 1078) performed meta-analyses of data from six prospective cohort studies and nine case–control studies published between January 1966 and March 2006. The authors examined stomach cancer risk based on increasing intake of processed meat for each type of study. The results from both types of study showed an increased risk of stomach cancer with a 30-gram increase of daily processed meat intake. The authors conclude that increased processed meat consumption is associated with an increased risk of stomach cancer. However, they warn that the association may be confounded or modified by other factors.
HIV-linked Nervous System Lymphoma and HAART
Primary central nervous system lymphoma (PCL) is a form of non-Hodgkin lymphoma that is confined to the craniospinal axis. PCL is rare in people with normal immune systems but is common among immunocompromized people, including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. To determine whether treatment with highly active antiretroviral therapy (HAART) altered incidence and outcomes of HIV-related PCL, Bower et al. (p. 1088) studied 9621 people infected with HIV, including 61 with HIV-related PCL. The authors found that patients treated in the HAART era had a lower incidence of PCL than patients treated in the pre-HAART era (1.2 per 1000 versus 3 per 1000) and longer overall survival. Patients' exposure to specific antiretroviral agents did not alter their risk for PCL. The authors conclude that HAART-induced improvements in immune system function benefit the central nervous system.
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