简介:High-performanceliquidchromatographic(HPLC)analysisoffluorouracil(5-FU)contentofthebloodandcolonofrabbitsisdescribed.Therewasnomarkeddifferenceintheplasma5-FUlevelandbloodconcentrationtimecurvefollowingintravenous(I.V.)(earvein)orintraarterial(I.A.)(inferiormesentericartery)injectionof5-FU15mg/kg.However,thedistributionof5-FUinthecolonafterIA.administrationwasquitedifferentthatafterI.V.administration.At10,20and30minutes,the5-FUcontentinthecolonwasshowntobe31-,17-and14-foldhigherwithI.A.thanwithI.V..ColonictissueAUCo-480min.was2453and690min/mg/mlrespectively(p<0.05).Itissuggestedthattoinject5-FUintoselectedarteriestotreatadvancedcolorectalcancermaybemoreusefulthanI.V.administration.
简介:Although5-fluorouracilisoneofthemostwidelyusedcytotoxicdrugsinthetreatmentofsolidtumorsinmanyorgans,ithasaseveredrawbackinitsseriousside-effects(e.g.gastrointestinalandbonemarrowtoxicity)andtheproperties(e.g.lowlipophilicity)leadingtovariousdeliveryproblems.Thelowlipophilicityof5-fluorouracilmaybeapredominantfactorforitspoorbiomembranepermeability.
简介:AbstractBackground:There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.Methods:We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.Results:Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).Conclusion:5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.
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简介:瞄准:评估intra动脉的5氟尿嘧啶(5-FU)的时间依赖为先进肝细胞癌(aHCC)的治疗。方法:有aHCC和肝肝硬化的37个成年日本病人与联合intra动脉的5-FU,cisplatin(CDDP),和甲酰四氢叶酸(LV)被对待。每个病人的日本综合阶段分数(JIS分数)是3或更多的。病人被划分成二个组,在组S的15个病人与6-h注入化疗在以后被对待(在12mg/h的LV,在10mg/h的CDDP,并且在250mg/m(2)的5-FU每4h)并且在组L的22个病人与24-h注入化疗(在12mg/h,在10mg/h的CDDP,和在每22h的250mg/m(2)的5-FU的LV)被对待。连续注入化疗经由合适的肝的动脉被执行为用一座植入的药水库的4wk的每5d。结果:有在化疗的4wk以后的部分回答的病人的百分比在组S是6.7%并且31.8%在组L。组L的幸存比组S的显著地好,与是的中部的生存时间在组L的496d和在组S的226d(P<0.05)。结论:连续24-hintra动脉的注入为aHCC是更有效的并且能显著地作为与6-h相比延长生存时间注入。