American Association for Cancer Research

January 15 Clinical Cancer Research Highlights

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Selected Articles from the January 15, 2007 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 January 15 issue of Clinical Cancer Research.


Reduced Folate Carrier Predicts Childhood ALL Outcomes 

Ge et al.
Page 451

The value of measuring expression of individual genes relevant to particular chemotherapy drugs as predictors of prognosis in pediatric acute lymphoblastic leukemia (ALL) remain controversial. Ge et al. used real-time RT-PCR to measure transcript levels for 20 genes relevant to chemo­therapy for pediatric B-precursor ALL in a case-control population of 91 patients. Only the human reduced folate carrier (hRFC) gene, encoding the major membrane transporter for methotrexate, showed a significant difference in median transcript levels between the 42 cases and the 49 controls. These results strongly suggest the prognostic importance of hRFC gene expression to treatment outcomes in pediatric ALL.


Taking a Closer Look at Sputum

Li et al.
Page 482

Li et al.The analysis of molecular genetic markers in biological fluids has been proposed as a powerful tool for cancer diagnosis. Li et al. previously defined genetic signatures of primary lung cancers by microarray-based comparative genomic hybridization analyses, providing potential biomarkers for the early detection of lung cancer. The results from the current study showed that there was high concordance between the genetic changes in paired sputum and tumor tissues from lung cancer patients. Detecting the signatures in sputum had higher sensitivity than that of sputum cytology for lung cancer diagnosis. These findings suggest that genetic changes may be new diagnostic markers and determination of the aberrations in sputum might be a complementary diagnostic tool for early stage lung cancer.

 


Methyl-Lexitropsin Toxic to Lethal Lesions

Bobola et al.
Page 612

Methyl-lexitropsin (Me-lex) is a methylating agent that binds to DNA, producing 3-methyladenine (3-meA) as the major (>90%) damage.  Bobola et al. now show that Me-lex is cytotoxic in 10 human glioma cell lines that differ in DNA repair capacity, demonstrating that 3-meA is a lethal lesion.  Unexpectedly, their data indicate that a factor(s) associated with expression of the DNA repair protein O6-methyl­guanine-DNA methyltransferase (MGMT), other than repair of O6-methylguanine, contributes to Me-lex sensitivity. Bobola et al. suggest that epigenetic changes accompanying the silencing of MGMT could be involved.  Me-lex may have clinical utility in the adjuvant therapy of gliomas. 


Prognostic Significance of Cyclin A1 Expression in Endoscopic Brushings 

Lao-Sirieix et al.
Page 659

Lao-Sirieix et al.It is currently not possible to predict which patients with Barrett’s esophagus are at greatest risk of progression to esophageal adenocarcinoma. This has profound implications for clinical follow-up programs. Lao-Sirieix et al. have shown in a nested case-control study that immunohistochemical detection of cyclin A expression can predict cancer progression. Furthermore, this analysis can be performed in cytological specimens or brushings, reducing the risks and time necessary for endoscopy. Application of this marker to endoscopic brushings could be used as a first step to identify patients with Barrett’s esophagus at highest risk of progression.