Improvement of insulin resistance by removal of systemic hydrogen peroxide by PEGylated catalase in obese mice.

Insulin resistance, a condition in which insulin action is impaired, is one of the characteristic features of type 2 diabetes. Excessive amounts of reactive oxygen species (ROS) interfere with the insulin signaling pathway, which leads to the progression of insulin resistance. To examine whether removal of systemic hydrogen peroxide is effective in improving insulin resistance, polyethylene glycol-conjugated catalase (PEG-catalase), a derivative with a long circulation half-life, was repeatedly injected into leptin-deficient ob/ob or high fat diet-induced obese mice for 16 or 10 consecutive weeks, respectively.

Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase.

Catalase delivery can be effective in inhibiting reactive oxygen species (ROS)-mediated acceleration of tumor metastasis. Our previous studies have demonstrated that increasing the plasma half-life of catalase by pegylation (PEG-catalase) significantly increases its potency of inhibiting experimental pulmonary metastasis in mice. In the present study, a biodegradable gelatin hydrogel formulation was used to further increase the circulation time of PEG-catalase.

Hydrogen peroxide-mediated nuclear factor kappaB activation in both liver and tumor cells during initial stages of hepatic metastasis.

Various factors involved in tumor metastasis are regulated by the transcription factor nuclear factor kappaB (NF-kappaB). Because NF-kappaB activation may contribute to establishment of hepatic metastasis, its activation in liver cells and tumor cells was separately evaluated in a mouse model of hepatic metastasis. pNF-kappaB-Luc, a firefly luciferase-expressing plasmid DNA depending on the NF-kappaB activity, was injected into the tail vein of mice by the hydrodynamics-based procedure, a well-established method for gene transfer to BALB/c male mouse liver.

SOD derivatives prevent metastatic tumor growth aggravated by tumor removal.

Although surgical removal is the most aggressive strategy to treat removable tumors, it sometimes aggravates tumor growth in metastatic sites. Because surgical procedures generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we examined whether the growth of micrometastasis is inhibited by superoxide dismutase (SOD) derivatives after surgical removal of tumors in mice. Murine melanoma B16-BL6 cells were inoculated into the footpad to establish spontaneous pulmonary metastasis.

Cationized catalase-loaded hydrogel for growth inhibition of peritoneally disseminated tumor cells.

A previous study demonstrated that ethylenediamine-conjugated catalase (ED-catalase) inhibits peritoneal dissemination of tumor cells in mice. To increase its inhibitory effects by sustained release, a hydrogel formulation of ED-catalase was prepared using a biodegradable hydrogel consisting of an acidic gelatin with an isoelectric point of 5.0.

Inhibition of peritoneal dissemination of tumor cells by cationized catalase in mice.

To inhibit peritoneal dissemination of tumor cells by destroying hydrogen peroxide, ethylenediamine-conjugated catalase (ED-catalase), a cationized derivative, was injected into the peritoneal cavity of mice. ED-catalase had about a 6-fold longer retention time within the cavity than unmodified catalase. Peritoneal dissemination was evaluated after intraperitoneal inoculation of B16-BL6/Luc, a melanoma clone stably expressing firefly luciferase, by measuring luciferase activity.

Analysis of in vivo nuclear factor-kappaB activation during liver inflammation in mice: prevention by catalase delivery.

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays crucial roles in inflammation, immunity, cell proliferation, and apoptosis. Until now, there have been few studies of NF-kappaB activation in whole animals because of experimental difficulties. Here, we show that mice receiving a simple injection of plasmid vectors can be used to examine NF-kappaB activation in the liver.

Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase.

Hydrogen peroxide may aggravate the peritoneal dissemination of tumor cells by activating the expression of a variety of genes. In this study, we used pegylated catalase (PEG-catalase) to examine whether prolonged retention of catalase activity within the peritoneal cavity is effective in inhibiting peritoneal dissemination in mouse models. Murine B16-BL6 cells or colon 26 cells labeled with firefly luciferase gene were inoculated intraperitoneally into syngeneic mice.

PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal.

Although surgical removal is a primary option for treating tumors, it can lead to the increased growth of metastatic tumors. Because surgical procedures may generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we investigated whether PEGylated catalase (PEG-catalase, plasma half-life of 13.6 h) was able to prevent this after surgical removal of a footpad tumor in mice.

Inhibition of peritoneal dissemination of tumor cells by single dosing of phosphodiester CpG oligonucleotide/cationic liposome complex.

Although unmethylated CpG dinucleotide-containing oligodeoxynucleotides (CpG ODN) are able to inhibit tumor metastasis through the induction of antitumor immunity, their stability and delivery to antigen presenting cells needs to be improved. In this study, we formulated a CpG ODN complex with cationic liposomes (CpG ODN-lipoplex) and its antitumor activity was evaluated in peritoneal dissemination models of tumor cells stably labeled with firefly luciferase gene. A single intraperitoneal administration of CpG ODN-lipoplex greatly reduced the number of tumor cells to 0.

Inhibition of metastatic tumor growth by targeted delivery of antioxidant enzymes.

To develop effective anti-metastatic therapy, targeted or sustained delivery of catalase was examined in mice. We found that mouse lung with metastatic colonies of adenocarcinoma colon26 cells exhibited reduced catalase activity. The interaction of the tumor cells with macrophages or hepatocytes generated detectable amounts of ROS, and increased the activity of matrix metalloproteinases.

Inhibition of metastatic tumor growth in mouse lung by repeated administration of polyethylene glycol-conjugated catalase: quantitative analysis with firefly luciferase-expressing melanoma cells.

Purpose: To develop a novel and effective approach to inhibit tumor metastasis based on controlled delivery of catalase, we first evaluated the characteristics of the disposition and proliferation of tumor cells. Then, we examined the effects of polyethylene glycol-conjugated catalase (PEG-catalase) on tumor metastasis. On the basis of the results obtained, PEG-catalase was repetitively administered to completely suppress the growth of tumor cells.

Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice.

Bovine liver catalase derivatives possessing diverse tissue distribution properties were synthesized, and their effects on hepatic metastasis of colon carcinoma cells were examined in mice. An intraportal injection of 1 x 10(5) colon 26 cells resulted in the formation of more than 50 metastatic colonies on the surface of the liver at 14 days after injection. An intravenous injection of catalase (CAT; 35000 units/kg of body weight) significantly (P < 0.