linoleic-acid and Peritoneal-Neoplasms

We evaluated the potential of a thermoresponsive hydrogel consisting of conjugated linoleic acid-coupled Pluronic F-127 (Plu-CLA) as a controlled release, intraperitoneal delivery system for docetaxel with the aim of treating peritoneal dissemination of gastric cancer. Previously, we established a peritoneal metastasis model that involves the injection of BALB/c mice with TMK1 human gastric cancer cells. One week after the TMK1 cells were injected, the mice were injected intraperitoneally with docetaxel alone or docetaxel-loaded Plu-CLA. Tumor progression and response to therapy were monitored by micro-positron emission tomography. The total number of peritoneal tumors and the ascites volume were also measured. Compared with docetaxel alone, the combination of docetaxel and Plu-CLA (docetaxel-Plu-CLA) significantly and synergistically reduced tumor cell survival. Docetaxel-Plu-CLA showed excellent anti-tumor activity, inducing apoptosis more potently than docetaxel alone. Docetaxel-Plu-CLA also significantly reduced the number of peritoneal metastatic nodules and increased survival in the peritoneal gastric cancer xenograft model. Our results show that intraperitoneal administration of docetaxel-Plu-CLA synergistically inhibits peritoneal metastasis and prolongs survival in a peritoneal gastric cancer model. Therefore, Plu-CLA is a potential intraperitoneal-route carrier for hydrophobic docetaxel for the effective treatment of peritoneal metastatic gastric cancer.

Topics: Animals; Antineoplastic Agents; Delayed-Action Preparations; Docetaxel; Hot Temperature; Hydrogels; Linoleic Acid; Male; Mice; Mice, Inbred BALB C; Nanocapsules; Peritoneal Neoplasms; Poloxamer; Stomach Neoplasms; Taxoids; Treatment Outcome

The effect on peritoneal metastasis of linoleic acid (LA) was examined using in vitro treatment of cancer cells and mouse peritoneal metastasis models. Firstly, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by LA in a dose-dependent manner with increment of apoptosis. LA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor gamma (PPARgamma) or 15-lipoxygenase-1, which converts LA to PPARgamma ligands. LA significantly inhibited invasion into type-IV collagen-coated membrane of MKN28 and Colo320 cells (p<0.05). BALB/c nu/nu mice inoculated with MKN28 and Colo320 cells into their peritoneal cavities were administrated with LA intraperitoneally (weekly, four times). The LA treatment significantly diminished the number of metastatic foci of both cells in the peritoneal cavity (p<0.05). Protein production in MKN28 and Colo320 cells treated with LA showed a decrease of epidermal growth factor receptor and an increase of Bax. These findings suggest that LA inhibits invasion and metastasis of human gastric and colon cancer cells by nondietary administration.

Topics: Animals; Antineoplastic Agents; Apoptosis; Arachidonate 15-Lipoxygenase; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Movement; Colonic Neoplasms; Cricetinae; Dose-Response Relationship, Drug; ErbB Receptors; Humans; Linoleic Acid; Lipoxygenase Inhibitors; Mice; Mice, Inbred BALB C; Mice, Nude; Oligodeoxyribonucleotides, Antisense; Peritoneal Neoplasms; PPAR gamma; Stomach Neoplasms; Xenograft Model Antitumor Assays

The fasting concentration of free fatty acids (FFA) in the ascitic fluid was determined in 14 patients with malignant ascites and in 19 patients with liver cirrhosis. In malignant ascites FFA levels were increased more than three times when compared with the levels in cirrhotic ascites (5.241 +/- 0.493 vs. 1.558 +/- 0.170 mumol/ml; P < 0.0001). Palmitic acid was the most representative saturated FFA (which together accounted for 2.499 +/- 0.323 vs. 0.833 +/- 0.064 mumol/ml; P < 0.0001), while unsaturated FFA (2.741 +/- 0.298 vs. 0.725 +/- 0.111 mumol/ml; P < 0.001) were represented, in decreasing order, by oleic, linoleic and arachidonic acids. The ratio of unsaturated to saturated FFA was higher in neoplastic patients (1.35 +/- 0.29 vs. 0.826 +/- 0.065 P < 0.05). Albumin concentration in ascitic fluid of neoplastic patients was 22.44 +/- 1.35 g/l, while that of cirrhotic patients was 8.19 +/- 0.32 g/l, P < 0.0001. A close relationship (R2 = 95.14%) between albumin concentration in ascitic fluid and levels of total FFA was found. These data support the hypothesis that the elevation of FFA in ascitic fluid allows discrimination between malignant and non-malignant ascites.

Topics: Adult; Aged; Albumins; Arachidonic Acid; Ascitic Fluid; Carcinoma, Hepatocellular; Fatty Acids, Nonesterified; Female; Humans; Linoleic Acid; Linoleic Acids; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Peritoneal Neoplasms