TY - JOUR
T1 - The antitumor effect of a thermosensitive polymeric hydrogel containing paclitaxel in a peritoneal carcinomatosis model
AU - Yu, Jieun
AU - Lee, Hyuk Joon
AU - Hur, Keun
AU - Kwak, Mi Kyung
AU - Han, Tae Su
AU - Kim, Woo Ho
AU - Song, Soo Chang
AU - Yanagihara, Kazuyoshi
AU - Yang, Han Kwang
PY - 2012/2
Y1 - 2012/2
N2 - The prognosis of peritoneal carcinomatosis is regarded as poor because safe, effective therapeutic modalities are lacking. Intraperitoneal chemotherapy is one treatment option, involving the delivery of a high concentration of chemotherapeutic drugs into the abdominal cavity, but the severe side effects associated with such treatment are a major obstacle in clinical application. We evaluated the anti-cancer effects of intraperitoneal delivery of a thermosensitive polymeric hydrogel containing chemotherapeutics in an animal model of carcinomatosis. The progress of peritoneal carcinomatosis, introduced by injecting a luciferasetransfected human gastric cancer cell line (HSC44Luc) into the peritoneal cavity of nude mice, was quantitatively evaluated by in vivo bioluminescence imaging. Three days after intraperitoneal (IP) injection of HSC44Luc cells, treatment solutions were injected into the peritoneal cavity. Mice were categorized into four groups depending on treatment method; these were (1) a control PBS group (n=5), (2) a hydrogel-only group (n=5), (3) a paclitaxel solution (30 mg/kg) group (n=3), and (4) a hydrogel-withpaclitaxel (15 mg/kg) group (n=5). Quantitative photon counting was performed weekly in each animal. Mice were sacrificed on the 5th or 28th day after treatment, for pathologic evaluation. In vivo bioluminescence imaging showed that photon counts in the hydrogel-with-paclitaxel and paclitaxel solution groups were significantly lower than in the PBS group over the entire experimental period. Although neither group of responding mice showed any peritoneal nodules on the 28th day after treatment, only the paclitaxel solution group exhibited dilated edematous changes in the intestine; these side effects were absent in animals treated with hydrogel-withpaclitaxel group. In conclusion, a thermosensitive hydrogel containing paclitaxel may be a safe and effective treatment option for peritoneal carcinomatosis.
AB - The prognosis of peritoneal carcinomatosis is regarded as poor because safe, effective therapeutic modalities are lacking. Intraperitoneal chemotherapy is one treatment option, involving the delivery of a high concentration of chemotherapeutic drugs into the abdominal cavity, but the severe side effects associated with such treatment are a major obstacle in clinical application. We evaluated the anti-cancer effects of intraperitoneal delivery of a thermosensitive polymeric hydrogel containing chemotherapeutics in an animal model of carcinomatosis. The progress of peritoneal carcinomatosis, introduced by injecting a luciferasetransfected human gastric cancer cell line (HSC44Luc) into the peritoneal cavity of nude mice, was quantitatively evaluated by in vivo bioluminescence imaging. Three days after intraperitoneal (IP) injection of HSC44Luc cells, treatment solutions were injected into the peritoneal cavity. Mice were categorized into four groups depending on treatment method; these were (1) a control PBS group (n=5), (2) a hydrogel-only group (n=5), (3) a paclitaxel solution (30 mg/kg) group (n=3), and (4) a hydrogel-withpaclitaxel (15 mg/kg) group (n=5). Quantitative photon counting was performed weekly in each animal. Mice were sacrificed on the 5th or 28th day after treatment, for pathologic evaluation. In vivo bioluminescence imaging showed that photon counts in the hydrogel-with-paclitaxel and paclitaxel solution groups were significantly lower than in the PBS group over the entire experimental period. Although neither group of responding mice showed any peritoneal nodules on the 28th day after treatment, only the paclitaxel solution group exhibited dilated edematous changes in the intestine; these side effects were absent in animals treated with hydrogel-withpaclitaxel group. In conclusion, a thermosensitive hydrogel containing paclitaxel may be a safe and effective treatment option for peritoneal carcinomatosis.
KW - Bioluminescence imaging
KW - Gastric cancer
KW - Paclitaxel
KW - Peritoneal dissemination
KW - Thermosensitive polymeric hydrogel
UR - http://www.scopus.com/inward/record.url?scp=84856513525&partnerID=8YFLogxK
U2 - 10.1007/s10637-010-9499-y
DO - 10.1007/s10637-010-9499-y
M3 - Article
C2 - 20669041
AN - SCOPUS:84856513525
SN - 0167-6997
VL - 30
SP - 1
EP - 7
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -
