Junya Yamasaki

Selective drug delivery to peri-tumoral region and regional lymphatics by local injection of aclarubicin adsorbed on activated carbon particles in patients with breast cancer???a pilot study

ACR-CH, which consists of aclarubicin (ACR) adsorbed onto activated carbon particles, was developed for locoregional chemotherapy for breast cancer. Thirty patients with breast cancer received an ACR (10 mg) injection intra- and peritumorally, either as ACR-CH or as ACR aqueous solution (ACR-AQ) 5 min before the operation for breast cancer. The ACR concentrations were significantly higher in the peritumoral regions and regional lymph nodes, and were also significantly lower in the blood plasma in patients given ACR-CH versus patients given ACR-AQ

Prevention of peritoneal metastasis of cancer with dextran sulfate???an experimental study in mice

Peritoneal metastases occur most often in the greater omentum, where tumor implantation sites are densely distributed. We used dextran sulfate (S-Dex) as an anti-cell-adherence agent to prevent i.p. seeded malignant cells from causing peritoneal metastases. S-Dex was tested for its anti-adherent activity against B-16 melanoma cells on plastic, and was examined for its ability to prevent implantation in the omentum and to improve survival in mice after B-16 melanoma was inoculated i.p. S-Dex prevented B-16 melanoma cells from adhering to the plastic wall. S-Dex reduced the number of B-16 melanoma cells implanted into the greater omentum and improved the survival of mice inoculated with B-16 melanoma cells. We conclude that S-Dex attenuated peritoneal metastases when B-16 melanoma cells were seeded i.p.

Dextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice.

Tumor recurrence is often seen at sites where the peritoneum has been injured during surgery for gastrointestinal malignancies. It is thought that malignant cells released from the tumor during surgery implant in the sites of injury in the abdominal wall and cause tumor recurrence. Here we use dextran sulfate (DS) as an antagonist to cell adhesion for preventing implantation of i.p. seeded malignant cells, thus suppressing the recurrent tumor formation often observed at the site of injury in postoperative abdominal walls. DS was tested for anti-adherent activity against B-16 melanoma cells to injured abdominal wall specimens ex vivo and showed the capacity to significantly impair B-16 melanoma cell adherence compared to controls without DS. DS was also tested for the activity to prevent i.p. seeded B-16 melanoma cells from implanting in the site of injury in the abdominal wall in vivo and DS prevented B-16 melanoma cells from implanting in the sites of injury in the abdominal wall. In the test for the activity to improve survival in mice after B-16 melanoma was inoculated i.p., DS improved the survival of mice as compared to the controls without DS. We conclude that DS may be useful in preventing surgically promoting tumor implantation at sites of injury in post-operative abdominal wall treated for gastrointestinal malignancies.

Therapeutic effects of 5-fluorouracil microspheres on peritoneal carcinomatosis induced by Colon 26 or B-16 melanoma in mice

The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an aqueous 5-FU solution and reduces toxicity. In this study, we evaluated the therapeutic effects of 5-FU-MS on peritoneal carcinomatosis in mice. Four days after an i.p. inoculation with Colon 26 or B-16 PC melanoma, 5-FU at 200 mg/kg was administered i.p. as 5-FU-MS or as an aqueous solution of 5-FU. 5-FU-MS extended the survival of mice bearing Colon 26 or B-16 PC melanoma significantly better than the equivalent dose of aqueous 5-FU solution.

Endoscopic local injection of a new drug delivery formulation, anticancer drug bound to carbon particles, for digestive cancers: Pilot study

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40–100mg peplomycin or 250–500mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12–64 months after therapy, or they died without evidence of cancer 12–98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

SELECTIVE DELIVERY OF 5-FLUOROURACIL (5-FU) TO I.P. TISSUES USING 5-FU MICROSPHERES IN RATS

A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.