blotting. Phosphorylated Dehydrogenase review STAT3 was not detected in any of the cell lines. ERK1/2 was phosphorylated to a barely detectable level with a tendency for higher phosphorylation in the more oxaliplatin resistant cell lines. AKT displayed an inverted bell shaped activation curve with the lowest phosphorylation level observed in S1 oxa4 and equally high phosphorylation observed in S1 and S1 oxa6. Discussion Two major mechanisms have been suggested for the cytostatic action of cetuximab direct inhibition of EGFR signalling through ligand binding competition, and activation of the immune system in the so called antibody dependent cellular cytotoxicity. In combination with, for example, tumour uptake issues, this limits the usefulness of elaborate in vitro studies to predict clinical effects of the substance.
However, cell experiments can GSK461364 929095-18-1 be used for the generation of hypotheses that can be further tested in clinical materials. In the present study, we were interested in the possibility of cells developing an increased sensitivity to cetuximab when acquiring resistance to oxaliplatin. To test this suggestion, we measured the cetuximab sensitivity in a set of five colon cancer cell lines, previously made resistant to oxaliplatin, and found a marked increase in the sensitivity to cetuximab with increasing oxaliplatin resistance. This has, to our knowledge, not been reported previously. We also found that increasing oxaliplatin resistance was accompanied by an increase in EGFR expression. These results suggest that EGFR signalling could be involved in acquired resistance to oxaliplatin.
A connection between resistance to platinum drugs and EGFR expression has been described in breast cancer cell lines. It has also been shown that EGFR signalling can increase DNA repair through up regulation of the DNA repair proteins, X ray repair complementing defective repair in Chinese hamster cells 1 and excision repair cross complementing rodent repair deficiency complementation group 1. In addition, several reports have indicated that EGFR expression can be up regulated by exposure to platinum drugs. In line with this, it was shown that cetuximab increased the effect of oxaliplatin in cell lines with acquiredsyndrome within 48 hours of the ischemic symptoms. Patients with non ST segment elevation acute coronary syndrome and those with ST segment elevation acute coronary syndrome who received optimal reperfusion therapy were eligible to enter the study.
Patients with non ST segment elevation acute coronary syndrome included those with non ST segment elevation myocardial infarction and those with unstable angina in whom conservative management was planned. Patients were also required to have an LDL cholesterol level 70 mg/dl and a fasting triglyceride level 500 mg/dl within 72 hours of symptom onset. Exclusion criteria included treatment for dyslipidemia with prescription medication within the preceding 4 weeks, current treatment with a depot formulation of progesterone or initiation of other hormone therapy within the previous 3 months, Q wave myocardial infarction, pulmonary edema, moderate or severe congestive heart failure, acute moderate to severe mitral regurgitation, acute ventricular septal defect, occurrence of ventricular fibrillation, sustained ventricular