The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Toshihiko Terao - One of the best experts on this subject based on the ideXlab platform.
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suppressing effects of dietary supplementation of soybean trypsin inhibitor on spontaneous experimental and peritoneal disseminated metastasis in mouse model
International Journal of Cancer, 2004Co-Authors: Hiroshi Kobayashi, Yoichi Fukuda, Ryuji Yoshida, Yasufumi Kanada, Setsuko Nishiyama, Mika Suzuki, Naohiro Kanayama, Toshihiko TeraoAbstract:The modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean trypsin inhibitor, as dietary supplements on experimental and spontaneous pulmonary metastasis of murine Lewis lung carcinoma 3LL Cells as well as peritoneal disseminated metastasis model in human ovarian cancer HRA Cells were investigated in i.v., s.c. and i.p. injection models in mice. Seven groups of female C57BL/6 or nude mice were fed a basal diet (control group) or the basal diet supplemented with KTI or BBI (5, 15, or 50 g/kg). Here we show that, in an in vivo spontaneous metastasis assay, the diet supplementation with KTI (15 and 50 g/kg), but not with BBI, for 28 days immediately after s.c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. The inhibition of lung metastasis was not due to direct antiTumor effects of KTI. In an in vivo experimental metastasis assay, the diet supplementation with KTI or BBI for 21 days after i.v. Tumor Cell Inoculation did not reduce the number of lung Tumor colonies. In addition, KTI (15 or 50 g/kg) treatment in a peritoneal disseminated metastasis model of HRA Cells resulted in a 40% reduction in total Tumor burden when compared with control animals. Immunoblot analysis revealed that KTI specifically reduced expression of uPA protein as well as phosphorylation of MAP kinase and PI3 kinase proteins in the Cells stimulated with agonists (G-CSF for 3LL Cells or TGF-β1 for HRA Cells). These results suggest that dietary supplementation of KTI more efficiently regulates the mechanism involved in the entry into vascular circulation of Tumor Cells (intravasation) than in extravasation during the metastatic process. KTI treatment may also be beneficial for ovarian cancer patients with or at risk for peritoneal disseminated metastasis; it greatly reduces Tumor burden in part by inhibiting phosphorylation of MAP kinase and PI3 kinase, leading to suppression of uPA expression. © 2004 Wiley-Liss, Inc.
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Inhibition of metastasis of Lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models.
International Journal of Cancer, 1995Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Mariko Itoh, Kinya Takeuchi, Toshihiko TeraoAbstract:: A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous lung metastases by murine Lewis lung carcinoma (3LL) Cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. UTI reduced lung Tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of lung metastasis. Inhibition of lung metastasis was not due to direct anti-Tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. Tumor Cell Inoculation inhibited metastatic lung Tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of Tumor Cells through Matrigel. UTI and peptide 3 inhibited neither Cell proliferation nor the binding of Tumor Cells to Matrigel and showed no significant suppression of chemotactic migration of Tumor Cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of Tumor Cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the metastatic process.
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Inhibition of metastasis of Lewis lung carcinoma by a synthetic peptide within growth factor-like domain of urokinase in the experimental and spontaneous metastasis model.
International Journal of Cancer, 1994Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko TeraoAbstract:: Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) Cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the metastatic migration process (extravasation from the bloodstream and then growth into pulmonary Tumor), none of the peptides introduced by i.v. single co-injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL Cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and Cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. Tumor Cell Inoculation, reduced the number of lung Tumor colonies. In a second in vivo assay that measures metastasis from a primary Tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17-34 for 7 days after s.c. Tumor Cell Inoculation significantly inhibited metastatic lung Tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of lung metastasis was not due to direct antiTumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL Cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by Tumor Cells to their receptor specifically reduced Tumor Cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of Tumor Cells into vascular circulation than extravasation during the metastatic process.
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Inhibition of the metastasis of Lewis lung carcinoma by antibody against urokinase-type plasminogen activator in the experimental and spontaneous metastasis model.
Thrombosis and Haemostasis, 1994Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko TeraoAbstract:: A selective inhibitory antibody, raised against human high molecular weight urokinase-type plasminogen activator (HMW-uPA), was examined to determine whether it would inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) Cells. Polyclonal antibody to human uPA cross-reacts with the murine uPA and inhibits murine uPA activity. When examined with an in vitro assay system using a modified Boyden chamber, the anti-catalytic IgG to uPA suppressed the invasion of Tumor Cells through Matrigel. Anti-uPA IgG inhibited neither the Cell proliferation nor the binding of Tumor Cells to Matrigel, and showed no significant suppression of chemotactic migration of Tumor Cells to fibronectin. In an in vivo spontaneous metastasis assay, multiple subcutaneous (s.c.) injections of anti-uPA IgG (up to a concentration of 200 micrograms [= 500 inhibitory unit/mouse/day] for 7 days immediately after s. c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. The inhibition of lung metastasis was not due to direct antiTumor effects of anti-uPA IgG. In an in vivo experimental metastasis assay, multiple s. c. injections of anti-uPA IgG for 7 days after intravenous (i. v.) Tumor Cell Inoculation did not reduce the number of lung Tumor colonies. These results suggest that uPA more efficiently regulates the mechanism involved in the entry into vascular circulation of Tumor Cells (intravasation) than in extravasation, during the metastatic process.
Hiroshi Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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suppressing effects of dietary supplementation of soybean trypsin inhibitor on spontaneous experimental and peritoneal disseminated metastasis in mouse model
International Journal of Cancer, 2004Co-Authors: Hiroshi Kobayashi, Yoichi Fukuda, Ryuji Yoshida, Yasufumi Kanada, Setsuko Nishiyama, Mika Suzuki, Naohiro Kanayama, Toshihiko TeraoAbstract:The modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean trypsin inhibitor, as dietary supplements on experimental and spontaneous pulmonary metastasis of murine Lewis lung carcinoma 3LL Cells as well as peritoneal disseminated metastasis model in human ovarian cancer HRA Cells were investigated in i.v., s.c. and i.p. injection models in mice. Seven groups of female C57BL/6 or nude mice were fed a basal diet (control group) or the basal diet supplemented with KTI or BBI (5, 15, or 50 g/kg). Here we show that, in an in vivo spontaneous metastasis assay, the diet supplementation with KTI (15 and 50 g/kg), but not with BBI, for 28 days immediately after s.c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. The inhibition of lung metastasis was not due to direct antiTumor effects of KTI. In an in vivo experimental metastasis assay, the diet supplementation with KTI or BBI for 21 days after i.v. Tumor Cell Inoculation did not reduce the number of lung Tumor colonies. In addition, KTI (15 or 50 g/kg) treatment in a peritoneal disseminated metastasis model of HRA Cells resulted in a 40% reduction in total Tumor burden when compared with control animals. Immunoblot analysis revealed that KTI specifically reduced expression of uPA protein as well as phosphorylation of MAP kinase and PI3 kinase proteins in the Cells stimulated with agonists (G-CSF for 3LL Cells or TGF-β1 for HRA Cells). These results suggest that dietary supplementation of KTI more efficiently regulates the mechanism involved in the entry into vascular circulation of Tumor Cells (intravasation) than in extravasation during the metastatic process. KTI treatment may also be beneficial for ovarian cancer patients with or at risk for peritoneal disseminated metastasis; it greatly reduces Tumor burden in part by inhibiting phosphorylation of MAP kinase and PI3 kinase, leading to suppression of uPA expression. © 2004 Wiley-Liss, Inc.
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Inhibition of metastasis of Lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models.
International Journal of Cancer, 1995Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Mariko Itoh, Kinya Takeuchi, Toshihiko TeraoAbstract:: A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous lung metastases by murine Lewis lung carcinoma (3LL) Cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. UTI reduced lung Tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of lung metastasis. Inhibition of lung metastasis was not due to direct anti-Tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. Tumor Cell Inoculation inhibited metastatic lung Tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of Tumor Cells through Matrigel. UTI and peptide 3 inhibited neither Cell proliferation nor the binding of Tumor Cells to Matrigel and showed no significant suppression of chemotactic migration of Tumor Cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of Tumor Cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the metastatic process.
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Inhibition of metastasis of Lewis lung carcinoma by a synthetic peptide within growth factor-like domain of urokinase in the experimental and spontaneous metastasis model.
International Journal of Cancer, 1994Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko TeraoAbstract:: Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) Cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the metastatic migration process (extravasation from the bloodstream and then growth into pulmonary Tumor), none of the peptides introduced by i.v. single co-injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL Cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and Cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. Tumor Cell Inoculation, reduced the number of lung Tumor colonies. In a second in vivo assay that measures metastasis from a primary Tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17-34 for 7 days after s.c. Tumor Cell Inoculation significantly inhibited metastatic lung Tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of lung metastasis was not due to direct antiTumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL Cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by Tumor Cells to their receptor specifically reduced Tumor Cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of Tumor Cells into vascular circulation than extravasation during the metastatic process.
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Inhibition of the metastasis of Lewis lung carcinoma by antibody against urokinase-type plasminogen activator in the experimental and spontaneous metastasis model.
Thrombosis and Haemostasis, 1994Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko TeraoAbstract:: A selective inhibitory antibody, raised against human high molecular weight urokinase-type plasminogen activator (HMW-uPA), was examined to determine whether it would inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) Cells. Polyclonal antibody to human uPA cross-reacts with the murine uPA and inhibits murine uPA activity. When examined with an in vitro assay system using a modified Boyden chamber, the anti-catalytic IgG to uPA suppressed the invasion of Tumor Cells through Matrigel. Anti-uPA IgG inhibited neither the Cell proliferation nor the binding of Tumor Cells to Matrigel, and showed no significant suppression of chemotactic migration of Tumor Cells to fibronectin. In an in vivo spontaneous metastasis assay, multiple subcutaneous (s.c.) injections of anti-uPA IgG (up to a concentration of 200 micrograms [= 500 inhibitory unit/mouse/day] for 7 days immediately after s. c. Tumor Cell Inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. The inhibition of lung metastasis was not due to direct antiTumor effects of anti-uPA IgG. In an in vivo experimental metastasis assay, multiple s. c. injections of anti-uPA IgG for 7 days after intravenous (i. v.) Tumor Cell Inoculation did not reduce the number of lung Tumor colonies. These results suggest that uPA more efficiently regulates the mechanism involved in the entry into vascular circulation of Tumor Cells (intravasation) than in extravasation, during the metastatic process.
Kazuhiko Machida - One of the best experts on this subject based on the ideXlab platform.
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SST-2 Tumor Inoculation is a useful model for studying the anti-Tumor immune response in SHR rats.
Environmental Health and Preventive Medicine, 2003Co-Authors: Naomi Nishio, Katsutaka Oishi, Kazuhiko MachidaAbstract:Objective The purpose of the present study was to investigate the relation between the dose of Tumor Cell Inoculation (especially the doses less than minimum required to evoke Tumor growth) and the anti-Tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes.
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SST-2 Tumor Inoculation is a useful model for studying the anti-Tumor immune response in SHR rats
Environmental Health and Preventive Medicine, 2003Co-Authors: Naomi Nishio, Katsutaka Oishi, Kazuhiko MachidaAbstract:Objective The purpose of the present study was to investigate the relation between the dose of Tumor Cell Inoculation (especially the doses less than minimum required to evoke Tumor growth) and the anti-Tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes. Method We inoculated rats with various doses of SST-2 Tumor Cells and examined natural killer (NK) Cell activity and lymphoblast formation in vitro . Result The results showed that the cytotoxicities against SST-2 Cells and lymphoblast formation of lymphocytes were enhanced by small dose Inoculation of Tumor Cells that could not induce Tumor growth. Conclusion It was suggested that was lymphocutes play an important role as an anti-Tumor immune system at small doses of Tumor Inoculation, which appears to reflect an early stage of Tumor growth in vivo . It was also suggested that SST-2 Tumor Inoculation might be a useful model for studying the anti-Tumor immune response in SHR rats.
Yoshitaka Fujii - One of the best experts on this subject based on the ideXlab platform.
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endostatin gene transfection using a cationic lipid advantages of transfection before Tumor Cell Inoculation and repeated transfection
Cancer Gene Therapy, 2004Co-Authors: Motoki Yano, Yoshiaki Nakashima, Yoshihiro Kobayashi, Kotaro Mizuno, Akimitsu Konishi, Hidefumi Sasaki, Ichiro Fukai, Ronald K Scheule, Yoshitaka FujiiAbstract:Intravenous endostatin gene transfection results in Tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma Cells. Mice were observed for 14 days following fibrosarcoma Cell Inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and Tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of Tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant Tumor suppression.
Martin Schabet - One of the best experts on this subject based on the ideXlab platform.
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Intrathecal therapy of leptomeningeal CEM T-Cell lymphoma in nude rats with anti-CD7 ricin toxin A chain immunotoxin
Journal of Neuro-Oncology, 1998Co-Authors: Ulrich Herrlinger, Rainer Buchholz, Heinz Schmidberger, Manfred Wehrmann, Daniel A. Vallera, Martin SchabetAbstract:We have established a new xenogeneic animal model of leptomeningeal metastasis (LM) by intracisternal Inoculation of human CEM T-Cell lymphoma into nude rats, and used it to evaluate the anti-lymphoma efficacy of an anti-CD7 ricin A chain immunotoxin (DA7). In vitro incubation with 2 μg/ml DA7 for 72 h inhibited CEM Cells by 90% in a trypan blue exclusion assay. To establish its anti-lymphoma activity, one and four days after cisternal Inoculation of 106 CEM Cells, eight animals each were treated cisternally with 10 μg DA7 in 50 μl PBS or sham-treated with 50 μl PBS. Histopathologically, all eight sham-treated and five of eight DA7 treated animals showed typical features of LM with multilayers of Tumor Cells along the whole subarachnoid space and the ventricular walls, as well as subependymal and diffuse parenchymal Tumor Cell infiltration. Three DA7 treated animals were free of Tumor. Two of these animals were asymptomatic long-term survivors (> 90 days). The third Tumor-free animal suddenly died on day 51. Histology revealed viral myocarditis. Median symptom-free survival was 51 days (range 29–90+ days) in DA7 treated and 34 days (range 29–87 days) in sham-treated animals (p=0.12, log-rank test). Histologically, no signs of neurotoxicity or systemic toxicity was found. However, DA7 treated animals showed a tendency to a slower weight increase on days 6–28 after Tumor Cell Inoculation. Our results indicate that this model is useful in studying leptomeningeal seeding and intracisternal treatment of lymphoma. The demonstrated anti-Tumor effect of DA7 treatment deserves further evaluation especially regarding the application of DA7 in early stages of LM from T-Cell lymphoma.
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Intrathecal treatment of C6 glioma leptomeningeal metastasis in Wistar rats with interlenkin-2
Journal of Neuro-Oncology, 1996Co-Authors: Ulrich Herrlinger, Rainer Buchholz, Piotr Jachimczak, Martin SchabetAbstract:The efficacy of intrathecal treatment of leptomeningeal metastasis (LM) with interleukin-2 (IL-2) was evaluated in an animal model using Wistar rats inoculated intracisternally with 10^7 C6 glioma Cells. Prior to the in vivo experiments the antiproliferative effects of human IL-2, and of murine IFN-γ and TNF-α which are cytokines induced by IL-2 were tested in a colony forming assay. Only IFN-γ caused a dose-dependent inhibition of colony formation. Twelve animals were treated intracisternally with either 10^5 IU IL-2 or control medium on day 0, 2, and 5 after Tumor Cell Inoculation. Both IL-2 treated and sham-treated animals developed LM with a symptom-free survival of 7 to 9 days. There was no significant difference between treated and untreated animals regarding time to onset of symptoms and pattern of Tumor growth. Infiltration of the Tumor tissue with ED-1+ monocytes and macrophages, and CD8+ lymphocytes, however, was slightly increased in IL-2 treated animals. In a second experiment 4 non Tumor-bearing Wistar rats were intracisternally injected with a single dose of 105 IU IL-2. These animals also showed slightly enhanced leptomeningeal infiltration with CD8+ lymphocytes compared to controls. We conclude that intrathecal application of high-dose IL-2 although eliciting a slight immune reaction within the leptomeninges does not inhibit leptomeningeal Tumor growth or prolong symptom-free survival in our animal model of LM. These results raise doubt about the clinical efficacy of intrathecal IL-2 treatment in patients with LM.
