| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© Oxford University Press 2007.
IN THIS ISSUE
Serum Vitamin D Levels and Subsequent Cancer MortalityEpidemiologic studies have suggested that higher vitamin D levels may be associated with lower mortality due to cancer. However, the relationship between measured vitamin D levels and total cancer mortality has not been examined in a prospective study. Freedman et al. (p. 1594) examined serum vitamin D levels in more than 16,000 participants in the third National Health and Nutrition Examination Survey and subsequent cancer deaths. Total cancer mortality was unrelated to serum vitamin D levels, but colon cancer mortality was lower among those with higher serum vitamin D levels.
In an editorial, Davis and Dwyer (p. 1563) point out that vitamin D levels may be closely linked to other dietary and lifestyle factors associated with colon cancer risk. Randomized clinical trials of the effects of vitamin D on the incidence of colonic polyps and invasive colon cancer are needed.
Differential Response of Epithelial Layers to Retinoic Acid Treatment
Retinoids are known to have antiproliferative and chemoprotective activity. Hittelman et al. (p. 1603) used biopsy specimens from former smokers participating in a randomized, placebo-controlled cancer prevention trial to determine whether a 3-month treatment with either 9-cis-retinoic acid (RA) or 13-cis-RA and 
-tocopherol could reduce cell proliferation in the bronchial epithelium. After either treatment, proliferative changes were found in the parabasal epithelial layer but not the basal layer. In analyses that used individual subjects as the unit, treatment with 13-cis-RA and -tocopherol, but not with 9-cis-RA, statistically significantly reduced cell proliferation. In analyses that used biopsy sites as the unit, both treatments statistically significantly reduced the frequency of highly proliferative biopsy sites in the parabasal layer. The authors conclude that different responses of the two epithelial layers were unexpected and warrant additional research.
In an editorial, Szabo (p. 1565) points out that use of the proliferation marker Ki-67 as a surrogate endpoint showed that the agents produced a biologic effect in their target site: the bronchial epithelium. However, before these agents can be evaluated in more advanced trials, more studies are needed of their mechanisms of action in the normal bronchial epithelium and the bronchial epithelium undergoing carcinogenesis.
Randomized Selection Trial of Four Prostate Cancer Therapy Regimens
Methods to select promising therapeutic agents for advanced trials are lacking. Thall et al. (p. 1613) conducted a randomized selection trial among patients with androgen-independent prostate cancer that used a multicourse treatment assignment algorithm. The algorithm tested four different chemotherapy regimens and took into account both first- and second-line treatments. Patients were evaluated every 8 weeks. Those responding continued on the same treatment, and those not responding were randomly assigned to another treatment. The endpoints were either a response or failure after two consecutive treatments. The most successful treatment was a weekly combination of paclitaxel, estramustine, and carboplatin (TEC). The most promising two-stage strategy was TEC followed by ketoconazole plus doxorubicin alternating with vinblastine plus estramustine. The authors conclude that some patients responded only to particular treatments and that responses to second-line treatments were not rare.
In a commentary, Bembom and van der Laan (p. 1577) review the available statistical methods to analyze data from sequentially randomized trials and present two different approaches to estimate success rates of different adaptive treatment strategies. They conclude that this novel trial design provides a rich source of information that is readily accessible through current analytical approaches.
Autocrine Factors, Glioma Invasion, and Paracrine Biology
Glial tumors recur due to the regrowth of invasive cells, which are unaffected by standard treatments. Factors that drive glioma invasion include signals propagated by secreted factors that signal through receptors on the tumor. These secreted factors are able to diffuse through the stroma around the tumor, thereby influencing parenchymal cells that surround the tumor mass. Conversely, normal brain parenchymal cells secrete ligands that can stimulate receptors on invasive glioma cells and potentially facilitate glioma invasion or create a permissive microenvironment for malignant progression. In a review, Hoelzinger et al. (p. 1583) describe candidate motility signals in glioma pathobiology, focusing on the contributions that specific ligand–receptor systems may make to the invasive phenotype of glioblastoma multiforme. The authors suggest that cells in the normal brain parenchyma be considered as potential targets for adjuvant therapies to control glioma growth and invasion because they are less likely to develop resistance than glioma cells.
SVV and Metastatic Neuroendocrine Cancer Treatment
Clinical trials have shown that oncolytic viruses are effective treatments for localized cancers. However, these viruses have not been as successful for the treatment of metastatic cancers when given systemically due to inactivation of the virus by the patient's blood or immune system and the inability of the virus to specifically target the tumor and not kill normal cells. To determine whether Seneca Valley Virus (SVV-001) could be used systemically to treat metastatic tumors, Reddy et al. (p. 1623) tested the activity of SVV-001 in human blood, normal and tumor cell lines, and immune-competent mice. They also treated immune-suppressed mice carrying tumor xenografts and metastases derived from human small-cell lung cancer and retinoblastoma cell lines against which the virus had strong cytolytic activity. SVV-001 activity was not inhibited by components in human blood, and the virus was well tolerated in immune-competent mice, even at high doses. SVV-001 was effective when delivered systemically to mice carrying tumor xenografts, yielding complete responses in the majority of the mice. The authors conclude that SVV-001 has potential for the systemic treatment of metastatic neuroendocrine cancers.
The Risk of Second Cancers in Cervical Cancer Survivors
Cervical cancer is the second most common malignancy in women worldwide. Chaturvedi et al. (p. 1634) evaluated the risk of second cancers among survivors based on registry data for more than 100,000 patients. Survivors were at an increased risk of smoking-related cancers and those related to human papillomavirus infection, including cancers of the pharynx, genital sites, and rectum/anus. Compared with the general population, women whose cervical cancer had been treated with radiation therapy had an increased risk of second cancers at heavily irradiated sites, and the increased risk persisted even after 40 years of follow-up.
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 1577-1582.
J Natl Cancer Inst 2007 99: 1583-1593.
J Natl Cancer Inst 2007 99: 1613-1622.
J Natl Cancer Inst 2007 99: 1623-1633.
J Natl Cancer Inst 2007 99: 1634-1643.
J Natl Cancer Inst 2007 99: 1594-1602.
J Natl Cancer Inst 2007 99: 1603-1612.
J Natl Cancer Inst 2007 99: 1565-1567.
J Natl Cancer Inst 2007 99: 1563-1565.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||