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Colorectal cancer (CRC) is the third leading cause of cancer mortality in the world. We report that one oncogene amplified on chromosome 3q26, LMO1, a master transcriptional regulator of stemness, operates to drive strong growth phenotype in CRC. The gene expression changes of LMO1 in human CRC tissues compared with noncancerous tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of LMO1 in CRC. Moreover, we discovered that LMO1 promoted cancer cell proliferation in vitro/in vivo and LMO1 expression correlated with elevated AKT phosphorylation in CRC while the AKT phosphorylation was required for oncogenic effects of LMO1. Next, our data point to the usefulness of LMO1 overexpression, as a new predictive marker for responsiveness to cetuximab. All in all, LMO1 is a commonly activated tumor promoter that activates AKT signaling in CRC and a new predictive marker for targeted therapy.

The release of in situ heavy metals (cadmium [Cd], copper [Cu], lead [Pb], manganese [Mn], and zinc [Zn]) from contaminated river sediment near a Cu-iron mine in South China was experimentally studied. The effects of pH values and the kinetics of heavy metal release were investigated. In addition, species of the 5 metals in the sediment were determined as a function of pH and time. Rates and extents of metal desorption were studied over 30 d, and a 3-parameter, 2-compartment model was used to analyze the desorption kinetics. The rate constants (k s ) for the slowly desorbing fraction of heavy metals were found to be 5 to 6 orders of magnitude lower than the corresponding rate constants (k r ) for the rapidly desorbing fraction, suggesting that slow desorption is the rate-limiting step. The partition coefficients (K d ) varied significantly among metals, on the order Pb > Cu >Zn > Cd > Mn, indicating that the sediment had a much higher retention capability for strongly hydrolyzed metals than for weakly hydrolyzed ones. The amount of metals released from the sediment decreased dramatically at the final pH of 2 to 4 and leveled off in the pH range of 5 to 8. Release time and pH exhibited a varied influence on the fractionation of metals, and had a more remarkable influence on more mobile fractions and hardly any effect on the residual fraction during the desorption process. The fractionation of strongly adsorbing metals like Pb was not as dependent on release time and pH as it was for the weakly bonded metals like Mn and Cd. The results indicate that in situ heavy metals may exhibit a sustainable potential for release and may increase health risks when the pH of the river is lowered. Environ Toxicol Chem 2019;38:464-473. C 2018 SETAC.