Cured meat products without direct addition of nitrate or nitrite: what are the issues?

The growing popularity of food products marketed in the United States as "natural" and "organic" has resulted in a proliferation of marketing efforts to meet consumer demands for these foods. Because natural and organic foods are not permitted to use chemical preservatives, the traditional curing agents used for cured meats, nitrate and/or nitrite, cannot be added to natural and organic processed meat products. However, alternative processes that utilize ingredients with high nitrate content, such as vegetable-based ingredients, and a nitrate-reducing starter culture can produce processed meats with very typical cured meat properties. Because it is not possible to analytically measure the amount of nitrite produced by this process, several potential issues deserve consideration. Regulations, for example, should permit labeling that accurately reflects the process and products, manufacturing procedures must be standardized to achieve product consistency, marketing efforts should clearly communicate the nature of these products to consumers, product quality must be maintained, and microbiological safety must be assured.

Breast cancer chemoprevention phase I evaluation of biomarker modulation by arzoxifene, a third generation selective estrogen receptor modulator.

PURPOSE: Arzoxifene, a new selective estrogen receptor modulator with strong breast antiestrogen activity and absence of uterine agonist activity, was explored as a potential chemoprevention agent. We performed a multi-institutional evaluation of arzoxifene in women with newly diagnosed ductal carcinoma in situ or T1/T2 invasive cancer. EXPERIMENTAL DESIGN: In a Phase IA trial, 50 pre- or postmenopausal women were randomized to 10, 20, or 50 mg of arzoxifene daily in the interval between biopsy and re-excision or were enrolled as no-treatment controls. In a Phase IB trial, 76 postmenopausal women were randomized to 20 mg of arzoxifene versus matched placebo. Serum specimens collected at entry and at re-excision were assayed for various hormones and growth factors. Tissue from biopsies (estrogen receptor + and/or progesterone receptor +) and re-excision specimens was evaluated immunohistochemically for proliferation (Ki-67 by MIB-1 and proliferating cell nuclear antigen) and other biomarkers. RESULTS: In both trials, increases in serum sex hormone binding globulin were noted, as were decreases in insulin-like growth factor (IGF)-I and the IGF-I:IGF binding protein-3 ratio (P < 0.007 versus control/placebo). For 45 evaluable women in Phase IA, decreases in proliferation indices were more prevalent for arzoxifene (particularly 20 mg) than for controls. For 58 evaluable women in Phase IB, a decrease in estrogen receptor expression for arzoxifene was observed compared with no change with placebo (P = 0.0068). However, decreases in proliferation indices for arzoxifene were not statistically different from placebo, perhaps due to a confounding effect of stopping hormone replacement therapy before entry. CONCLUSION: Given the favorable side effect profile and the biomarker modulations reported here, arzoxifene remains a reasonable candidate for additional study as a breast cancer chemoprevention agent.

Her-2/neu gene amplification in ductal carcinoma in situ of the breast.

This study evaluated the relative frequencies of HER-2/neu gene amplification in ductal carcinoma in situ (DCIS)-associated invasive breast cancer and DCIS alone. We examined archival tissue samples of 100 DCIS lesions with an invasive component (cases) and 100 without an invasive component (controls), with cases and controls matched by pathologic nuclear grade. HER-2/neu gene amplification was determined by fluorescence in situ hybridization. We compared HER-2/neu gene amplification in DCIS lesions only, irrespective of the presence or absence of an invasive component. HER-2/neu gene amplification occurred significantly less frequently in the cases (26%) than in the controls (40%), with an odds ratio of 0.35 (95% confidence interval, 0.17-0.72; P < 0.004) after adjustment for pathologic and quantitative-image-analyzed morphometric nuclear grade. The HER-2/neu gene also was amplified more frequently in higher- than in lower-grade DCIS alone (56% versus 19%, respectively; P < 0.0001) or in higher- than in lower-grade DCIS with invasive cancer (44% versus 2%, respectively; P < 0.00001). Future studies should examine the potential roles of HER-2/neu and other biomarkers (e.g., p21 and Rb) as markers of the risk of DCIS patients for invasive breast cancer and as molecular targets of chemoprevention in breast intraepithelial neoplasia.

The efficacy of 9-cis-retinoic acid (aliretinoin) as a chemopreventive agent for cervical dysplasia: results of a randomized double-blind clinical trial.

9-Cis-retinoic acid (aliretinoin) is a pan-retinoid receptor agonist and has been demonstrated in preclinical models to have potent chemoprevention effects. The purpose of this study was to determine the utility of using aliretinoin as a chemoprevention agent in cervical dysplasia. Patients with histological evidence of cervical intraepithelial neoplasia (CIN) 2/3 were randomized in a double-blind manner to receive high-dose aliretinoin (50 mg), low-dose of aliretinoin (25 mg), or placebo daily for 12 weeks. Compliance and side effects were monitored at various time points during therapy. At the completion of therapy, all of the patients underwent a loop procedure. Histology of pretreatment biopsies was compared with that of loop specimens. One-hundred and fourteen patients with CIN 2/3 were enrolled in the study. In the 112 patients evaluable for toxicity, headache was the most common clinical side effect and was experienced more frequently (74%) in the high-dose aliretinoin group. Eight patients withdrew from the study before completion of study medication because of unacceptable side effects. In the 104 patients evaluable for efficacy, there was no statistical difference in the rate of regression among the placebo (32%), the low-dose aliretinoin (32%), and the high-dose aliretinoin (36%) groups. (P = not significant; power 0.06). Aliretinoin at these dosages and this schedule does not appear to result in significant regression rates in CIN 2/3 patients when compared with placebo. Headache is encountered frequently and may thwart efforts to increase the dose or duration of aliretinoin in future cervical cancer chemoprevention studies. The rate of histological regression in biopsied CIN 2/3 patients is high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size in cervical dysplasia chemoprevention studies.