American Association for Cancer Research

July 1 Cancer Research Highlights

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Selected Articles from the July 1, 2006 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 Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the July 1 issue of Cancer Research.


Proteomic Profiles Differ for Polyps, Colorectal Carcinomas

Polley et al.
Page 6553
Research on the adenoma-carcinoma sequence has focused mainly on tumors, with less attention paid to early changes in the normal-appearing mucosa. Polley et al. applied proteomics to the colorectal mucosa of patients with and without neoplasia. Statistical analysis demonstrated that patterns of protein expression in flat mucosa from healthy subjects differed significantly from that of patients with polyps or carcinomas. Recognition and further characterization of these field changes may provide novel protein biomarkers of vulnerability to colorectal cancer, and suggest new mechanisms underlying the role of diet and other environmental factors in its causation.

 


IGF-IR Targeting Compounds Prevent Neuroblastoma/Bone Interaction

van Golen et al.
Page 6570

CAN 07-01-06 vanGolen 6570The type I insulin-like growth factor receptor (IGF-IR) is involved in tumor progression in multiple cancers. In the pediatric tumor neuroblastoma, tumorigenic cells express high levels of the IGF-IR. Since bone expresses abundant IGF ligands, van Golen et al. investigated the potential involvement of IGF-IR in neuroblastoma bone metastasis. Neuroblastoma cells expressing high IGF-IR levels interact with cellular components of bone and, in mice, target to and from osteolytic tumors within bone tissue. Two IGF-IR–directed therapeutic compounds, a small molecule inhibitor, and a monoclonal antibody prevent neuroblastoma cell interaction with bone.


iNKT-Licensed B Cells Trigger Strong Antitumor Immunity

Chung et al.
Page 6843

CAN 07-01-06 Chung 6843Due to poor immunogenic properties, the B-lymphocyte has been ignored as a source of cellular vaccine for antitumor immunotherapy. To overcome this disadvantage, Chung et al. developed a new vaccine with B-lymphocytes loaded with natural killer T-cell ligand and tumor-derived peptide. Mice receiving this vaccination successfully generated peptide-specific cytotoxic memory immunity. The antitumor activity induced by this B-lymphocyte–based vaccine in tumor-bearing mice was as efficient as those induced by dendritic cell vaccination in several tumor models. These results show promise as the basis of an alternate cellular vaccine against tumors as well as infectious diseases.

 

 

 


Immune Response Genes Predominant among Esophageal Dysplasia Profile

Joshi et al.

Page 6851

Molecular targets associated with regression and progression of esophageal squamous dysplasia, a precursor to esophageal squamous cell carcinoma, have not been identified. To address this gap, Joshi et al. used microarray analysis to assess changes in gene expression in normal esophageal mucosa of individuals whose dysplasia regressed, was stable, or progressed. One hundred forty-nine differentially expressed genes were found, including 20 associated with regression and 129 associated with progression. Immune response genes were the most prominently over-represented pathway. These results suggest an important role for immune response in the natural history of dysplastic lesions and identify potential gene targets.


Oncogene Mutations in Plasma DNA of Healthy Subjects

Gormally et al.

Page 6871

CAN 07-01-06 Gormally 6871Free DNA fragments are detectable in the plasma of healthy subjects as well as cancer patients. In patients, this free DNA often contains alterations identical to those often found in tumor DNA (mutations, hypermethylations, deletions, amplifications) suggesting that part of this material is of tumoral origin. Gormally et al. have used the set-up of a large prospective study, the European Prospective Investigation into Cancer and Nutrition, to develop a nested case-control study aimed at assessing the significance of plasma DNA mutations in TP53 or KRAS2 in the plasma DNA of healthy subjects for subsequent cancer occurrence. They report that mutations are present in a small number of healthy subjects, and are detectable ahead of bladder cancer diagnosis. These observations have implications for using plasma DNA in monitoring early steps of carcinogenesis.