• Archives of Pharmacal Research
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• 제23권2호
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• pp.167-171
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• 2000

We have investigated the in vitro cytotoxic effect of liposome-encapsulated N-(phospho-nacetyl)-L-aspartic acid (PALA) against C-26 murine colon cancer cells, and have compared it in this regard to free PALA. Three different PALA-containing liposomal formulations using distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and polyethyle-neglycol-derivatized distearoylphosphatidylethanolamine (PEG-DSPE) were made and their cytotoxicity was measured. In 72 hr continuous exposure experiment with C-26 cells, the 50% growth inhibitory concentration ($IC_50$) of DSPG-PALA liposome formulation was $0.09\mu\$, which showed about 65-fold more potent than unencapsulated free PALA ($5.1\mu\$). Similar degree of increase in cytotoxicity was also observed in 1 hr exposure experiment. However the $IC_50$ of PEG-DSPE-PALA liposome and DSPC-PALA liposome were $10.7\mu\$and $11.8\mu\$respectively, which showed slightly less potent than unencapsulated free PALA. Physical characteristics of PALA-liposomes, such as the size and drug:lipid ratio were also determined. In conclusion, negatively-charged DSPG-PALA liposome showed the highest cytotoxic effect among tested on the C-26 cells in vitro.

• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.127-131
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• 2000

Previously, we have reported an antitumor efficacy of liposomal N-(phosphon-acetyl)-L-aspartic acid (or PALA) in C-26 tumor bearing Balb/c mice, where PALA in liposome was administered one day after tumor inoculation. In this report, we have investigated the therapeutic potency of liposomal formulation of PALA, which was administered eight days after tumor inoculation in the same C-26 tumor bearing mice. The C-26 murine colon tumor inoculated mice were randomized for the in vivo therapy and the survival was measured after a single intraperitoneal injection of the drug. When the therapy was initiated eight days after tumor inoculation, DSPC-PALA at 150 mg/kg resulted in a significant increase in median survival time (MST) of 56% over the control group which received MES/HEPES buffer alone. However, none of the free PALA and DSPG-PALA liposome doses caused a statistically significant increase in MST over control group at the 95% confidence level. At 750 mg/kg dose, free PALA caused a marginally significant improvement in MST by 34%, but both 375 mg/kg and 150 mg/kg doses of free PALA caused only a 2% and a 4% increase in MST, respectively. These results show that PALA in neutrally charged liposome can exhibit considerably greater potency than free PALA in established C-26 tumor bearing mice.

• Journal of Pharmaceutical Investigation
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• 제30권1호
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• pp.39-45
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• 2000

We have investigated the efficacy of liposome encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) for the treatment of the C-26 murine colon tumor in Balb/c mice, and have compared it in this regard to free PALA. Healthy female Balb/c mice and C-26 tumor inoculated mice were randomized for the maximum tolerated dose (MTD) study and the in vivo therapy study, and the survival was measured after a single intraperitoneal injection of the drug. The maximum tolerated dose for intraperitoneally administered drug was found to be 750 mg/Kg for free PALA, and was greater than the maximum dose possible (150 mg/Kg) for PALA encapsulated in both DSPC and DSPG liposomes. When drug was administered one day after tumor implantation, 150 mg/Kg of PALA in DSPG liposomes increased the percentage of tumor bearing mice surviving at day 36 from 8% (buffer control) to 88%. In contrast, 150 mg/Kg free PALA increased the day 36 surviving percentage to only 25%. A 150 mg/Kg dose of PALA in DSPC liposomes increased the surviving percentage to 50%, while a 75 mg/Kg dose of PALA in sterically stabilized liposomes increased the surviving percentage to 78%. These results show that PALA in negatively charged or sterically stabilized liposomes can exhibit considerably greater potency than free PALA in C-26 tumor bearing mice.

• Archives of Pharmacal Research
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• 제26권10호
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• pp.861-867
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• 2003

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

• Nutrition Research and Practice
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• 제4권1호
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• pp.30-35
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• 2010

Our study focused on the antioxidant activities of Mosidae leaf ethanol extract (MLE) and included measurements of reducing power, total phenolic compounds, DPPH radical scavenging activity, and hydroxyl radical scavenging activity. In order to determine whether or not MLE evidences any chemopreventive activities, experimental lung metastasis was induced via the i.v. inoculation of colon26-M3.l carcinoma cells into BALB/c mice. Additionally, we attempted to characterize any possible cytotoxic effects in murine normal splenocytes and tumor cells (B16-BL6 and colon26-M3.1). The total phenolic content and reducing capacity were measured at 39 mg/100 mL and 1.24, respectively, whereas the DPPH and hydroxyl radical scavenging activities of MLE were measured to be 88.89% and 22.10%, respectively. Prophylactic i.v. treatment with MLE resulted in a dose-dependent and significant inhibition of lung metastasis. Specifically, a MLE dose of 200 ug per mouse resulted in an 88.90% inhibition of lung metastasis. For the cytotoxicity assay, MLE doses up to 100 ug/mL were not shown to affect the growth of normal murine splenocytes. Additionally, the survival of normal cells was not affected at MLE doses below 500 ug/mL. However, MLE doses up to 500 ug/mL reduced the percentage of tumor cell growth for B16BL6 (67% alive) and colon26-M3.1 (62% alive) cells.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.148.2-149
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• 2003

The inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum), on tumor metastases produced by highly metastatic murine tumor cells, B 16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, was investigated in syngeneic mice. (omitted)

• Archives of Pharmacal Research
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• 제25권4호
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• pp.522-527
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• 2002

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.