<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">YOSHIDA, ERI</style></author><author><style face="normal" font="default" size="100%">KUDO, DAISUKE</style></author><author><style face="normal" font="default" size="100%">NAGASE, HAYATO</style></author><author><style face="normal" font="default" size="100%">SUTO, AKIKO</style></author><author><style face="normal" font="default" size="100%">SHIMODA, HIROSHI</style></author><author><style face="normal" font="default" size="100%">SUTO, SHINICHIRO</style></author><author><style face="normal" font="default" size="100%">KAKIZAKI, IKUKO</style></author><author><style face="normal" font="default" size="100%">ENDO, MASAHIKO</style></author><author><style face="normal" font="default" size="100%">HAKAMADA, KENICHI</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">4-Methylumbelliferone Decreases the Hyaluronan-rich Extracellular Matrix and Increases the Effectiveness of 5-Fluorouracil</style></title><secondary-title><style face="normal" font="default" size="100%">Anticancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018-10-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">5799-5804</style></pages><doi><style  face="normal" font="default" size="100%">10.21873/anticanres.12919</style></doi><volume><style face="normal" font="default" size="100%">38</style></volume><issue><style face="normal" font="default" size="100%">10</style></issue><abstract><style  face="normal" font="default" size="100%">Background/Aim: Pancreatic cancer responds poorly to most chemotherapeutic agents. Several studies have reported that hyaluronan (HA)-rich extracellular matrix (ECM) is a biological barrier against chemotherapeutic agents. 4-methylumbelliforone (MU) led to inhibition of HA synthesis and its preservation in ECM, which may enhance 5-fluorouracil (5-FU) cytotoxicity. Thus, new therapy with MU and 5-FU may be developed for pancreatic cancer. Materials and Methods: A 5-fluorouracil (5-FU) concentration and 4-methylumbelliferone (MU) dosage was analyzed by high-performance liquid chromatography (HPLC). Change in antitumor efficacy of 5-FU in combination with MU was also examined in vivo and in vitro. Results: Combined 5-FU and MU treatment inhibited cell proliferation better than 5-FU alone; 0.01 mM 5-FU alone decreased cell proliferation by 37.7 %, while 0.01 mM 5-FU with 0.5 mM MU decreased cell proliferation by 57.4%. MU enhanced the intracellular concentration of 5-FU by 47.3% compared to control. Mice tumors treated with 5-FU and MU decreased in size and animal survival was prolonged. Moreover, MU decreased cohesiveness of the intercellular space. Conclusion: Combination therapy of 5-FU with MU was effective. A novel therapy can be designed for pancreatic cancer by using ECM modulation.</style></abstract></record></records></xml>