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Matsui M.,Aichi Cancer Center Research Institute | Shimizu Y.,Biomedcore Inc. | Kodera Y.,Nagoya University | Kondo E.,Aichi Cancer Center Research Institute | And 2 more authors.
Cancer Science | Year: 2010

We recently developed a novel drug delivery system (DDS) using oligomannose-coated liposomes (OMLs), which are effectively taken up by mouse peritoneal macrophages to carry anticancer drugs to omental milky spots known as initial metastatic sites in the peritoneal cavity in mice. However, the feasibility of the clinical application of this DDS to gastric cancer patients remains essentially unknown. In the present study, we investigated whether human peripheral blood monocytes (PBMs) and human peritoneal macrophages (PEMs) could successfully uptake OMLs and deliver them to the micrometastatic foci in the mouse omentum and resected omentum from cancer patients ex vivo. When OMLs were incubated with the PBMs from four healthy volunteers in vitro, an average 88% of CD14-positive PBMs, most of which also express CD206, took up OMLs, and this uptake was significantly inhibited by α-methylmannoside. In the experiment using PEMs obtained from peritoneal washes of five gastric cancer patients, the average uptake rate (63%) of OML by CD14-positive PEMs was somewhat lower than that of PBMs, but in three advanced gastric cancer patients the uptake rate of OMLs was 76% which was comparable to that of mouse PEMs. Oligomannose-coated liposome (OML)-incorporated PBMs and PEMs were successfully accumulated at the micrometastatic foci at the omentum formed after intraperitoneal injection of GFP-tagged gastric cancer cells into mice. Furthermore, OML-incorporated PBMs substantially accumulated to tumor foci in the surgically resected human omentum ex vivo. These results suggest that OMLs using human monocytes/macrophages as a cellular vehicle have the potential to target peritoneal micrometastasis in the omentum of gastric cancer patients. © 2010 Japanese Cancer Association.

Toray Engineering Co. and Biomedcore Inc. | Date: 2010-08-24

Disclosed are: an apparatus which enables the easy production of liposomes having uniform particle diameters; and others. Specifically disclosed is a liposome production apparatus comprising: a microtube having a flow path through which a lipid-dissolved solution comprising at least one lipid, water and a water-miscible organic solvent can pass; a housing section in which the microtube is accommodated; and a cooling means for cooling the dissolved solution contained in the microtube in the housing section to a temperature at which liposomes can be produced. The apparatus enables the production of liposomes having uniform particle diameters.

Mizuuchi M.,Sapporo Medical University | Hirohashi Y.,Sapporo Medical University | Torigoe T.,Sapporo Medical University | Kuroda T.,Sapporo Medical University | And 4 more authors.
Experimental and Molecular Pathology | Year: 2012

The aim of this study was to establish an efficient human papilloma virus (HPV) type 16-targeting cancer immunotherapy. Persistent high-risk HPV infection causes cervical intra-epithelial neoplasia (CIN) and subsequent cervical carcinoma. HPV type16 (HPV16) is one of the common carcinogenic types and is found in about 50% of invasive cervical carcinomas. HPV16-derived viral proteins E6 and E7 are expressed in cancerous cells through the progression of the disease and have a role in carcinogenesis but are not expressed in normal cells. Thus, these proteins are regarded as ideal antigens for cervical carcinoma immunotherapy. In this study, we generated a novel HPV 16 E6 and E7 gene plasmid containing oligomannose liposomes (OML-HPV). We compared the cytotoxic T lymphocyte (CTL) induction efficiency of OML-HPV and that of standard liposome-HPV16 E6 and E7 DNA complex. HPV16 E6-specific CTLs could be generated from HPV 16-positive cervical carcinoma patient's peripheral blood mononuclear cells (PBMCs) by stimulating OML-HPV, but could not by stimulating standard liposome-HPV 16 E6, E7 DNA complex. Furthermore, we screened HLA-A24-restricted HPV16 E6- and E7-derived peptides, and found that one E6-derived peptide (E6 66-74) showed the highest immunogenicity with ELISPOT assay from 100% of HPV16-positive patients (4 out of 4). On the other hand, other E6- or E7-derived peptides, including E6 49-57, E6 82-90, E6 87-95, E6 98-106 and E7 83-93, showed less frequent reactivity. These results indicate that OML-HPV is a more effective approach than DNA vaccination using standard liposomes, and that a novel HLA-A24-restricted peptide, E6 66-74, might be a suitable target of cervical cancer immunotherapy. © 2011 Elsevier Inc.

Yamakami K.,National Defense Medical College | Tsumori H.,National Defense Medical College | Sakurai Y.,National Defense Medical College | Shimizu Y.,Biomedcore Inc. | And 2 more authors.
Pharmaceutical Biology | Year: 2013

Context: Dental caries are an infectious oral bacterial disease caused by cariogenic streptococci. These streptococci inhabit dental biofilms which comprise insoluble glucans. Objective: To prevent dental caries, nisin, a suitable agent active against Gram-positive bacteria, was examined in vitro for its ability to suppress insoluble glucan-biofilm synthesis by cariogenic streptococci. Materials and methods: To investigate glucan-biofilm synthesis by a typical cariogenic streptococcus, Streptococcus mutans 10449, the naked form of nisin was loaded onto a 96-well microplate in vitro model. To prolong the efficacy of nisin as a preventive agent, liposome-encapsulated nisin (nisin-liposome) was examined for its ability to inhibit the synthesis of glucan-biofilms on microplates. Results: Naked nisin (100 pmol) completely suppressed insoluble glucan-biofilm synthesis by S. mutans 10449 following 1 h cultivation in 96-well microplates. The concentration of nisin-liposome required for the efficacious inhibition of glucan-biofilm synthesis was four times lower than that of naked nisin following 2 h cultivation. In particular, nisin-liposome (30 pmol nisin equivalent) prolonged the inhibitory activity of nisin against glucan-biofilm synthesis by S. mutans 10449 for up to 6 h, while naked nisin (30 pmol) gradually lost this inhibitory activity over the same period. In vitro release assay of nisin from the liposome showed that 76% nisin was released within 6 h. Discussion and conclusion: The findings indicate the usefulness of nisin-liposome for the sustained release of nisin. Thus, nisin-liposome could play a potential role in preventive medicine as an inhibitor of the glucan-biofilm synthesis. © 2013 Informa Healthcare USA, Inc.

Biomedcore Inc. | Date: 2013-05-23

Methods and compositions for treating or preventing type 2 diabetes by inhibiting expression or activity of monoacylglycerol O-acyltransferase 1 (MOGAT1) are disclosed. Also disclosed are methods to identify such compositions.

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