American Association for Cancer Research

October 1 Clinical Cancer Research Highlights

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Selected Articles from the October 1, 2005 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the October 1 issue of Clinical Cancer Research.


CD40 Ligand Vaccine Induces Transient Immune Response in Patients

Biagi et al.
Page 6916

CCR 10-01-05 Biagi 6916Human CD40 ligand enhances the antigen-presenting capacity of B-CLL cells. Autologous B-CLL cells expressing hCD40L and human IL-2 were prepared. Nine patients were enrolled. A B-CLL–specific response was detected in seven patients. Biagi et al. observed that the frequencies of IFN-g, granzyme-B, and IL-5 spot-forming cells showed a significant rise over the frequency before vaccination. Nonetheless, these responses were transient. High levels of immunoregulatory T cells were present and their in vitro removal increased the antileukemic reactivity. These results suggest that immune responses to B-CLL can be obtained with autologous vaccines, but that removal of immunoregulatory T cells in vivo may be necessary to sustain the antitumor immune response.


Obesity, Weight Gain, and Rising PSA Linked to Prostate Cancer Progression

Strom et al.
Page 6889

In a follow-up study of 526 prostatectomy patients, Strom et al. determined that men who experienced biochemical failure (e.g., rising PSA) were heavier and had higher body mass index (BMI) at age 25, 40, and diagnosis. Obesity at diagnosis predicted biochemical failure independently of clinical characteristics. Additionally, weight gain of greater than 1.5 kg/yr between age 25 and diagnosis was associated with significantly shorter time to biochemical failure. A new nomogram incorporating BMI improves its predictive utility. These results validate the importance of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited.


Genistein Reverses Hypermethylation of Genes

Fang et al.
Page 7033

CCR 10-01-05 Fang 7033Genistein, the major isoflavone from soy, has been shown to have cancer preventive activity, but the mechanisms are not clearly understood. Fang et al. demonstrate that treatment of human esophageal cancer cells with genistein (2–20 mmol/L) caused the reversal of hypermethylation and reactivation of retinoic acid receptor β, p16INK4a, and O6-methylguanine methyltransferase genes. Similar activity is also observed with human prostate cancer cells. Greater extent of reactivation is observed when genistein is combined with low concentrations of trichostatin, sulforaphane, or 2’-deoxy-5-aza-cytidine. Reversal or prevention of the hypermethylation of key genes by genistein may contribute to its cancer prevention activity.


CEA and Ep-CAM Enable Detection of Serous Effusion Tumor Cells

Passebosc-Faure et al.
Page 6862

Cytological diagnosis of malignancy in serous effusions is often hampered by low number of tumor cells and by delicate distinction from inflammatory or mesothelial cells. To improve the detection sensitivity of tumor cells, Passebosc-Faure et al. evaluated a panel of molecular markers in 114 effusions. Combined together, CEA and Ep-CAM enabled detection of tumor cells in 63% of cytologically negative malignant effusions and, in the whole population of effusions, the detection sensitivity increased from 73% (cytology alone) to 90% (cytology + RT-PCR) with 100% specificity. This marker-based analysis provides a clinically reliable and noninvasive test for the diagnosis of malignancy.