American Association for Cancer Research

August 1 Clinical Cancer Research Highlights

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Selected Articles from the August 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 August 1 issue of Clinical Cancer Research.


XAGE-1 Likely as Target Antigen for Lung Adenocarcinoma Immunotherapy

Nakagawa et al.
Page 5496

XAGE-1 is a CT-like antigen identified by searching the EST database. Within four transcript variants, XAGE-1b was shown to be a dominant antigen recognized by sera from cancer patients. Nakagawa et al. investigated the expression of XAGE-1 transcript variants by conventional and real-time RT-PCR and XAGE-1 protein expression by immunohistochemistry in non-small cell lung cancer specimens. Sera from the patients were analyzed for XAGE-1b antibody production by ELISA assay and Western blot. The results showed that XAGE-1b is highly and strongly expressed in lung adenocarcinoma and is immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.

 


Bortezomib Appears to Disrupt Hypoxia Response in Solid Tumors

Mackay et al.
Page 5526

The 26S proteasome disassembles many proteins involved in cancer growth. Preclinical data using proteasome inhibitors including bortezomib suggest this represents a novel therapeutic target, although the critical proteins disrupted in cancer patients are uncertain. To address this, Mackay et al. obtained sequential biopsies from liver metastases during a phase II clinical trial treating colorectal cancer patients with bortezomib. Whereas there was a trend for accumulation of hypoxia-inducible factor–1α, which is degraded via the proteasome, there was a striking decrease in the HIF-1 transcriptional target carbonic anhydrase IX, suggesting that bortezomib acts to disrupt the hypoxia response in solid tumors.


NF-κB Inhibitor Limits IL-6 Levels, Cachexia in Prostate Cancer Model

Kuroda et al.
Page 5590

Kuroda et al. undertook studies to evaluate the association between IL-6 and cachexia, and an inhibitory effect of a new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in prostate cancer. Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in progressive prostate cancer patients. DHMEQ caused a significant decrease in serum IL-6 levels and an improvement of cachexia in the mice. These results suggest an association between serum IL-6 and cachexia and that a new NF-κB inhibitor, DHMEQ could prevent the development of cachexia presumably through the inhibition of IL-6 secretion.

 


Non-Smokers’ Lung Cancer Features Gene Hypermethylation

Hsu et al.
Page 5410

The importance of identifying factors involved in non-smoking lung cancer has long been recognized. Hsu et al. reported results from a gene/protein analysis of DNA mismatch repair genes, hMLH1 and hMSH2, in 105 non-smoking female non-small-cell lung cancer (NSCLC) patients. Of these tumors, 67% and 30% had lost expression for hMLH1 and hMSH2 protein, respectively, and promoter hypermethylation seemed to be the predominant cause. Moreover, hMSH2 promoter hypermethylation appeared to be a biomarker for poor prognosis. This is the first report of an association of hMLH1 and hMSH2 promoter hypermethylation in non-smoking NSCLC tumorigenesis.