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The Korea National Information Center for the 3Rs was established in August 2011, to enhance humane science and animal welfare in Korea. It is a national Three Rs platform, with the goal of exchanging knowledge and sharing examples of best practice, in order to help replace laboratory animal use in education and training. This paper briefly summarises the progress made and the challenges that have become apparent during the initial operation of the collaborative project. There is a need to recognise and manage the challenges resulting from policy changes, especially misinterpretation of the objectives by the decision makers at the participating academic institutions and the government. The collective power of this type of collaborative project can be used to leverage an ongoing commitment to essentials such as consistent funding for operational and support staff, as well as allocation of the required space.

Objective.Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary.

Several studies have shown that nitric oxide (NO)-releasing agents can kill tumor cells. Unfortunately, currently available NO delivery molecules do not target tumor cells preferentially. To exploit the overexpression of glucose transport proteins and the high level of glucose transport characteristics of tumor cells, glucose was conjugated to S-nitroso-N-acetyl-penicillamine (2-gluSNAP) and evaluated for cytotoxicity in human ovarian carcinoma cells. The cytotoxicity of 2-gluSNAP and SNAP was assessed by clonogenic cell survival assays performed in A2780S (cisplatin sensitive) and A2780cP (cisplatin-resistant) ovarian carcinoma cells in vitro. Immunoblotting and immunohistochemistry were used to assess the expression of Glut-1 hexose transport protein in the cell lines as well as in paraffin blocks from 28 surgical specimens of epithelial ovarian carcinoma. Apoptosis was assessed by an end-labeling assay. The ovarian carcinoma cell lines consistently were more sensitive to 2-gluSNAP than SNAP alone. The median effective doses (MEDs) for 2-gluSNAP and SNAP in the A2780s cell line were 0.0042 μM and 20.4 μM, respectively. Therefore, 2-GluSNAP was nearly 5000-fold more potent than the NO-donating moiety (SNAP) alone. In the A2780cP cells, the MED for 2-gluSNAP (0.38 μM) was 250-fold lower than that for SNAP alone (100 μM). Immunoblotting and immunohistochemistry studies showed overexpression of Glut-1 in the cell lines and in 23 of 28 epithelial ovarian carcinoma specimens. The novel glyco-NO conjugate 2-gluSNAP exhibits a much greater cytotoxicity than the parent NO donor without the hexose moiety. These agents have the potential to target tumor cells preferentially, that overexpress Glut-1. This transporter is expressed highly in epithelial ovarian carcinoma. Cancer 2000;88:381–8. © 2000 American Cancer Society.

lnterleukin-1 α (IL-1 α ) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 α in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 αat varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 α (0.5 μg/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 α injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 α on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), gran-ulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 α as a generalized stimulator of hematopoiesis and show that the cytokine-induced suppression of late-stage erythropoiesis can be prevented by EPO.

Summary Changes in tumor cell proliferation and chemosensitivity after partial (up to 3/4) surgical resection were studied in C3H/HeJ mammary tumors, In all studies surgical cytoreduction stimulated tumor cell proliferation in the residual tumor, as evidenced by increases in the3H-TdR labelling index between 24 and 72 hrs after surgery. The time of maximal proliferative activity was directly related to the amount of tumor removed. In spontaneous mammary tumors, proliferative recovery after 1/2 resection could be delayed by giving dexamethasone 24 hrs after resection. The regrowth delay after surgery and various combinations of dexamethasone, vincristine, 5-FU, and cyclophosphamide, was used to assess the significance of the kinetic changes in the residual tumor for the design of adjuvant therapeutic strategies.

Ein ungeschützter und intakter Kohlenhydratrest wurde erstmalig in einen Übergangsmetallkomplex eingebaut. Der kohlenhydratgebundene Platin(II)-Komplex cis-Dichlor[(2-β-D-glucopyranosidyl)propan-1,3-diamin]platin (Struktur siehe Abbildung) ist ein Cisplatin-Analogon und weist eine ähnliche Antitumorwirksamkeit bei zugleich verbesserter Löslichkeit in Wasser auf.

An unprotected and intact carbohydrate moiety has been observed for the first time in a transition metal complex. The carbohydrate-linked platinum(II) complex cis-dichloro[(2-β-D-glucopyranosidyl)propane-1,3-diamine]platinum (see picture) is an analogue of cisplatin and exhibits comparable antitumor activity along with increased solubility in water.

Tumor necrosis factor (TNF), a protein synthesized in response to the endotoxin bacterial lipopolysaccharide (LPS), is the classical mediator of acute hemorrhagic necrosis of tumors. We have demonstrated that interleukin-la (IL-lα), with a spectrum of activities very similar to those of TNF, also causes acute hemorrhagic necrosis of tumors. Both TNF and IL-1 induce a cascade of events including the synthesis or release of each other. The present studies were thus undertaken to determine whether the hemorrhagic necrosis induced in tumors by IL-lα is due to TNF. Kinetic parameters of IL-lα-induced hemorrhage were similar to those observed with recombinant murine TNF-α (TNF-α) or LPS in RIF-1 fibrosarcomas in C3H/HeN (endotoxin-sensitive) mice. However, the amount of TNF found in the sera or tumors of animals treated with LPS was more than 20-fold higher than in mice treated with IL-lα, and LPS induced similar degrees of hemorrhagic necrosis, which was measured by determining the packed volume of red blood cells by 59Fe labeling. A low but significantly hemorrhagic dose of IL-lα induced no detectable TNF in tumors. Pretreatment with 250 μg of neutralizing antibody to TNF had no effect on IL-lα-induced hemorrhage, whereas TNF-α- and LPS-induced hemorrhagic effects were significantly reduced. These results demonstrate an important antitumor activity of IL-αa that appears to be independent of TNF. [J Natl Cancer Inst 83:842–848,1991]