The Basic Study of Liposome in Temperature-Sensitive Gel at Body Temperature for Treatment of Peritoneal Dissemination

Peritoneal dissemination is a disease that is difficult to treat surgically because it is widely scattered and proliferates in the abdominal cavity. It is a challenge that even if the drug is administered directly into the abdominal cavity, it rapidly disappears from the abdominal cavity, and the therapeutic effect is not optimal, as expected. In this study, for a liposomal paclitaxel in temperature-sensitive gel that is a suspension before administration and a gel after intraperitoneal administration, the antitumor effect of this formulation was evaluated. Temperature-sensitive gels were prepared using methylcellulose, sodium citrate, and macrogol 4000 and mixed with liposomal paclitaxel. Liposomal paclitaxel containing temperature-sensitive gel in the body was administered into the peritoneal cavity of a mouse model of peritoneal dissemination; the number of cells was significantly reduced compared to a paclitaxel solution of liposomal paclitaxel. These results showed that the liposome in temperature-sensitive gel inhibited cell proliferation in the abdominal cavity. This formulation can be administered easily at room temperature, and it gels and remains in the abdominal cavity for a long period, resulting in a more substantial effect than the existing drug

Effects of a single-dose administration of Bowman-Birk inhibitor concentrate on anti-proliferation and inhabitation of metastasis in M5076 ovarian sarcoma bearing mice

The present study was designed to investigate the effects of Bowman-Birk inhibitor concentrate (BBIC) on anti-proliferation, up-regulation of Connexin 43 (Cx43) expression and inhabitation of hepatic metastasis in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x10^6 cells/animal) were subcutaneously transplanted into the back of BDF_1 mice. The ‘pre-treated’ (n=10) and ‘post-treated’ (n=10) groups were fed a standard diet (CE-2) compounded with 0.5% BBI from 3 weeks before and from the day of tumor inoculation, respectively, until 4 weeks after tumor inoculation. The ‘control group’ (n=10) was fed CE-2 alone. Relative tumor weights in the pre- (0.013±0.010) and post- (0.012±0.013) treated groups were significantly reduced by 30.0 and 32.5%, respectively, as compared to the control group (0.040±0.022, p<0.01). The relative densities of Cx43 mRNA and Cx43 protein were significantly higher in the BBIC-treated groups than in the control group. The median numbers of macroscopic spontaneous metastases were significantly lower in the pre- (1.0±2.3) and post- (1.9±3.6) treated groups than in the control group (71.4±97.3). These results suggest that BBIC reduces proliferation as a result of increased expression of Cx43 genes in mice with M5076 ovarian sarcoma. In addition, BBIC inhibits hepatic metastasis in M5076-bearing mice

Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice

The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x10^5 cells/animal) were subcutaneously transplanted onto the backs of BDF_1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anti-carcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway