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View the Table of Contents for the July 15 issue of Cancer Research.
Hennig et al. Page 6011
Pancreatic intraepithelial neoplasias (PanINs) are the precursor lesions of pancreatic adenocarcinoma. To date no specific markers for PanINs have been described. Hennig et al. found that 5-lipoxygenase (5-LOX) is expressed in PanINs in human pancreas, a transgenic mouse model of early disease and in a hamster carcinogenic model of pancreatic cancer, but not in normal pancreatic ductal cells. Overexpression of 5-LOX stimulates cell growth and increases the sensitivity of the cells to 5-LOX inhibitors. Therefore, 5-LOX may serve not only as a marker for PanINs but also as a possible target for pancreatic cancer prevention.
Chan et al. Page 6029
The roles of microRNAs—small non-coding regulatory RNA molecules—in lineage determination, cell proliferation, and genomic location suggests that microRNAs could be important factors in development or maintenance of the neoplastic state. Using a homemade oligonucleotide array, Chan et al. identified a microRNA that is markedly up-regulated in human brain tumors, glioblastomas. Sequence-specific knock-down of this microRNA triggered activation of caspases and led to increased apoptotic death of glioblastoma cells in culture. These findings suggest that aberrantly expressed microRNAs may function as micro-oncogenes by blocking, for example, expression of key apoptosis-enabling genes.
Brueckner et al. Page 6305
The clinical use of DNA methyltransferase inhibitors in chemotherapy has been limited by their low specificity and inherent cytotoxicity. Brueckner et al. have now characterized a novel small molecule, RG108, that represents the first rationally designed DNA methyltransferase inhibitor. RG108 inhibited DNA methyltransferase activity both in a cell-free in vitro system and in human tumor cell lines. The compound was also able to demethylate and reactivate epigenetically silenced tumor suppressor genes and thus holds substantial promise for further development in epigenetic cancer therapies.
Ishibashi et al. Page 6450
Gender-dependent factors were postulated in development of non-small cell lung cancers (NSCLCs), but the involvement of specific steroid receptor family members remains unclear. Ishibashi et al. examined progesterone receptor (PR) in NSCLCs. PR immunoreactivity was detected in 46.5% of NSCLCs, and was associated with better clinical outcome of the patients. Cell proliferation was inhibited by progesterone in PR-positive NSCLC cells (A549, LCSC#2, and 1-87) in a dose-dependent manner, and tumor volume of these cells injected into nude mice was also dose-dependently inhibited by progesterone. These results suggest that PR is a potent prognostic factor in NSCLCs, and progesterone may be effective in suppressing development of PR-positive NSCLCs.
Schwarzbaum et al. Page 6459
Previous studies find that people who report allergic conditions have lower primary adult malignant brain tumor rates, but these results may be attributed to recall bias. Schwarzbaum et al. compared the prevalence of six polymorphisms that increase susceptibility to asthma and other allergic conditions in 111 glioblastoma multiforme (GBM) cases and 422 population-based controls. GBM are the most common adult primary malignant tumor. They find that four of these polymorphisms (two on IL-4RA and two on IL-13 precursor genes) are associated with GBM. Furthermore, each of these polymorphism-GBM associations is in the opposite direction of a corresponding polymorphism-asthma and allergic condition association. These findings suggest that the previously reported association between allergic conditions and GBM may be valid.