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Akira Kito, Jun Yoshida, Naoki Kageyama, Nakao Kojima and Kunio Yagi

tumor cells selectively, it is necessary to develop new antitumor drugs or drug delivery systems which have selectivity toward glioma cells. Liposomes are artificially generated lipid vesicles which entrap drugs within their aqueous compartment and/or lipid bilayer membranes. 1 They have been regarded as a promising drug delivery system for the treatment of cancer that increases the antitumor effect and decreases the side effects of antitumor drugs. 3, 11, 17 Targeting of liposomes to specific cells by means of monoclonal antibodies (MAb's) has been tried by

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Tali Siegal, Aviva Horowitz and Alberto Gabizon

brain tumors are exposed to subtherapeutic levels of chemotherapy because most agents are given as a bolus and have short distribution half-lives, resulting in a slim chance to circulate through the tumor vascular bed. Liposome-based anticancer chemotherapy may offer the advantage of reduced systemic toxicity combined with selective drug delivery into tumor. Recent studies revealed that new formulations of small-sized (< 100 nm), longcirculating liposomes (also referred to as Stealth or sterically stabilized liposomes) appear to offer selective tumor localization

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Kenichi Kakinuma, Ryuichi Tanaka, Hideaki Takahashi, Masato Watanabe, Tadashi Nakagawa and Mizuo Kuroki

M alignant glioma responds poorly to chemotherapy, presumably because antitumor drugs cannot be delivered in effective concentrations to the tumor site without causing complications and because the existence of the blood-brain barrier (BBB) restricts the distribution of many antitumor drugs to malignant gliomas. Thermosensitive liposomes are microscopic vesicles composed of phospholipid bilayers capable of containing drugs. These liposomes are designed to remain relatively stable in the bloodstream at physiological temperatures and to release the drugs they

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Peter J. Dickinson, Richard A. Lecouteur, Robert J. Higgins, John R. Bringas, Byron Roberts, Richard F. Larson, Yoji Yamashita, Michal Krauze, Charles O. Noble, Daryl Drummond, Dmitri B. Kirpotin, John W. Park, Mitchel S. Berger and Krystof S. Bankiewicz

systems have been described that facilitate image-guided CED. These have included MR imaging systems with T2-weighted imaging correlated with 123 I-labeled serum albumin single photon emission computed tomography, 29 , 30 and liposomes colabeled with Gd. 13 , 21 , 26 , 27 , 35 Liposomes are phospholipid nanoparticles composed of a bilayered membrane capable of encapsulating a variety of therapeutic molecules. Liposomal encapsulation of a variety of drugs, including chemotherapeutics, has been shown to result in prolonged half-life, sustained release, and decreased

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Takashi Tashiro, Jun Yoshida, Masaaki Mizuno and Kenichiro Sugita

being applied to increase cytotoxicity. As to the mechanism for killing neoplastic cells by LAK cells, both direct LAK cell-neoplastic cell contact lysis 7 and the secretion of cytotoxic factors from LAK cells 17 are involved. In addition, there have been several reports that tumor necrosis factor (TNF)-α plays an important role in the cytotoxicity of LAK cells through its release from these cells. 1, 11, 17 In the present study, we transfected the TNF-α gene into LAK cells by means of our novel liposomes 13, 14, 21 and investigated whether the cytotoxicity of LAK

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Atsushi Saito, Hiroaki Shimizu, Yusuke Doi, Tatsuhiro Ishida, Miki Fujimura, Takashi Inoue, Hiroshi Kiwada and Teiji Tominaga

via the accumulation of oxLDL in endothelial cells and smooth muscle cells, the activation of inflammatory cells, and activation of downward MMP cell signaling pathways. 2 The liposomal drug-delivery system is a novel effective strategy to achieve efficient therapeutic outcome through the reduction of side effects. It is likely that the delivery system will be applied to a variety of diseases. The benefits of liposome include its slow drug-releasing effects and drug-targeting effects on lesions with surface attachments (for example, antibodies, as in the present

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Vanja Varenika, Peter Dickinson, John Bringas, Richard LeCouteur, Robert Higgins, John Park, Massimo Fiandaca, Mitchel Berger, John Sampson and Krystof Bankiewicz

study, we do show that leakage occurs even in experienced hands and needs to be visualized to adequately adjust treatment. This analysis may help a neurosurgeon decide the best course of action to take at the onset of such leakages. Our results may also explain some of the failures of CED in clinical trials, as many investigators have not visualized the infusions and therefore would not have noticed spontaneous leakages. 9 , 12 , 13 Methods Liposome Preparation Liposomes containing an MR imaging contrast agent were composed of DOPC/cholesterol/PEG-DSG with a

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Michal T. Krauze, Ryuta Saito, Charles Noble, Matyas Tamas, John Bringas, John W. Park, Mitchel S. Berger and Krystof Bankiewicz

, 5, 10, 20, 21 Agarose gel findings were translated into a study in the rat brain and then in the nonhuman primate (Macaca fascicularis) brain by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Materials and Methods Reflux-Free Step-Design Cannula First, metal cannula needles of various diameters (18–32 gauge) were evaluated in an agarose gel model to assess the flow rate at which reflux occurred. The design used in the animal studies consisted of a 27-gauge cannula needle (Terumo Medical Corp

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Benjamin K. Hendricks, Aaron A. Cohen-Gadol and James C. Miller

convection-enhanced delivery involves microinfusions of an agent with micropumps for targeted delivery to the brain parenchyma, and this approach depends on hydrostatic pressures, diffusion, and efflux from the capillaries. 73 Examples of delivery agents used are nanoparticles, liposomes, viral vectors, and immunotoxins. 160 Convection systems, though intuitively attractive, result in heterogeneous distribution of these agents, impedingly high interstitial fluid pressure, rapid efflux from the injection site, 118 , 128 and they may also result in neurotoxicity. 43 A

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Masaaki Mizuno, Jun Yoshida, Toru Takaoka and Kenichiro Sugita

-inhibiting effect of in vitro transfection of glioma cells with HuIFN-γ; gene entrapped in the liposomes and also evaluated the usefulness of combining liposomal transfection and adoptive immunotherapy using LAK cells. Materials and Methods Cell Lines Cells of the SK-MG-1 and U-251 MG human glioma cell lines were used in this study. The cells were maintained in Eagle's minimum essential medium supplemented with 10% fetal calf serum, 2 mM nonessential amino acids, 5 mM L-glutamine, and antibiotic agents (streptomycin, 100 µg/ml, and penicillin, 100 U