Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

Objective：To investigate the effects of E7080 and N5-（1-iminoethyl）-L-ornithine dihydrochloride （L-NIO）on colorectal cancer alone and in combination.Methods：HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis （xCELLigence system） was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane （CAM） model.Results：We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration （IC50） value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71％ of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions：Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.

Paroxetine overdose during pregnancy

Paroxetine is a selective serotonin reuptake inhibitor(SSRI)used in the treatment of depression and anxiety disorders.In some epidemiological studies,slightly increased risks of major malformations and cardiac malformations have been reported following paroxetine exposure in the first trimester of pregnancy.However,such findings have been inconsistent.There is only one report of any overdose of an SSRI during pregnancy,and that involved escitalopram.The aim of this case report was to describe the impact of a paroxetine overdose in the first trimester of pregnancy on the health of the foetus.A 21-year-old mother of one child who was pregnant with a second child was prescribed 20 mg/day paroxetine hydrochloride for the treatment of anxiety/depression.The patient ingested 15 or 1620-mg tablets of paroxetine hydrochloride(300-320 mg)during the 5th week of pregnancy as a suicide attempt.Within 15 min of ingestion,she was admitted to hospital and treated for intoxication.No evidence of maternal SSRI intoxication was observed after treatment.The patient consulted our teratology information service for further risk assessment regarding possible major congenital malformations following the paroxetine overdose.We were unable to find previous reports of paroxetine overdose during pregnancy in the literature.The timely administration of the overdose treatment and the lack of maternal intoxication symptoms were considered positive for the foetal well-being,and the patient was referred for perinatology and psychiatry follow-ups.A healthy,3500-g male infant was born at 38 weeks’gestation,and his development at the age of 2 years was normal.This is the first reported case of paroxetine overdose during pregnancy.Comprehensive studies are needed to evaluate pregnancy outcomes after SSRI overdose.