5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency.

BACKGROUND: Colorectal cancer is (CRC) one of the commonest cancers and its therapy is still based on few drugs. Currently, no biological criteria are used to choose the most effective of the established drugs for treatment. METHODS: A panel of 77 CRC cell lines was tested for sensitivity to 5-fluorouracil (5FU) using the SRB assay. The responses were grouped into three categories and correlated with genetic changes in the cell lines. RESULTS: The strongest and most clearcut correlation was between 5-fluorouracil response and replication error status (mismatch repair deficiency). All the other significant correlations (loss of heterozygosity for DCC and mutations in TGFbIIR) are secondary to the association with replication error status. INTERPRETATION AND CONCLUSION: Our findings validate previous analyses based mainly on clinical data, and indicate that replication error status could be a useful guide to 5-fluorouracil-based CRC therapy. Essentially, all previously described correlations with 5FU response are secondary to the association with replication error status.

Serum neuron-specific enolase in human status epilepticus.

Neuron-specific enolase (NSE) is a sensitive marker of brain injury after stroke, global ischemia, and coma. We report changes in serum NSE (s-NSE) in 19 patients who sustained status epilepticus. s-NSE peaked within 24 to 48 hours after status epilepticus. The mean peak s-NSE level for the entire group was elevated compared with the levels for normal controls (24.87 ng/ml versus 5.36 ng/ml, p = 0.0001) and for epileptic controls (24.87 ng/ml versus 4.61 ng/ml, p = 0.0001). The mean peak s-NSE level for the 11 subjects without an acute neurologic insult (15.44 ng/ml) was also significantly increased compared with levels for normal and epileptic controls. Further, s-NSE was significantly correlated with outcome and duration. We conclude that s-NSE is a promising in vivo marker of brain injury in status epilepticus and warrants further study in larger populations.

Neuron-specific enolase is increased after nonconvulsive status epilepticus.

Serum neuron-specific enolase (s-NSE), a marker of brain injury and acute seizures, was increased in 2 patients with nonconvulsive SE. Neither patient had an acute neurologic insult other than nonconvulsive SE (NCSE) accounting for s-NSE changes. Increase in s-NSE provides further in vivo evidence of transient brain injury after NCSE.

The Water Pressure Integrity Test--a new integrity test for hydrophobic membrane filters.

Sterilizing grade hydrophobic filters are used for the sterile filtration of gases in pharmaceutical and biological applications. Until now the integrity of these membrane filters and their ability to retain bacteria, has been correlated to a solvent based nondestructive integrity test. Current methods use solvents to wet the membranes in order to perform bubble point and diffusion integrity tests. Solvent based integrity tests make it difficult to test in situ following sterilization because of the risk of downstream solvent contamination. A newly developed method, the Water Pressure Integrity Test (WPIT), allows for the integrity testing of hydrophobic filters eliminating the problems associated with traditional test methods employing solvents. A prime advantage of WPIT is that it may be performed in situ post sterilization without any downstream manipulations. The test has been directly correlated to the retention of bacterial challenges. Data will be provided to show the reliability and sensitivity of this easy to perform test.