LPS-induced antitumoral effects on glioblastoma multiforme are mediated, in part, by the Tlr-4 receptor. Further understanding of this process may lead to novel treatment strategies for this uniformly fatal disease.

We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.

Intratumoral injections of LPS caused dramatic regression of subcutaneously implanted delayed brain tumor cell mouse gliomas. Investigation of this antitumoral effect may improve treatment responses for patients with malignant gliomas.

The utility of clinical magnetic resonance contrast media (MRCM) in the evaluation of pathologies within the central nervous system (CNS) is well established (1-9). Bloodbrain-barrier (BBB) disruption in tumors and other lesions of the CNS is attributable to abnormal endothelial junctions, and is a key feature of the aggressive neovascular formations within malignant tumors. This characteristic of BBB disruption accounts for the increased enhancement of intracranial tumors on MRI after administration of MRCM, which is helpful in delineating tumor anatomy. For gliomas, increased enhancement is suggestive, although not absolutely indicative, of an increased histological grade of malignancy. Degrees of tumor malignancy previously have been assessed in animal models using covalently Gd-conjugated macromolecule-based MRCM as MRI signal enhancers (3-6). However, these covalently-bound Gd-macromolecules have not been studied in clinical trials in humans. Hence, the available low-molecular-weight extracellular MRCM are now exploited under dynamic protocols for tumor assessment (7-9). These agents extravasate into extracellular space throughout non-CNS tissues, and thus present a limited time window at high concentration for the detection of CNS tumors. Despite successes achieved with the extracellular agents to date, the need for intravascular agents that would extravasate only in the face of BBB disruption continues to be advocated as a next step in improving the diagnostic utility of these and related techniques (10,11).Noncovalent albumin-binding Gd-chelates represent a new class of agents. These agents, unlike the covalently bound Gd-macromolecules, are small chelates with side chains that undergo reversible noncovalent interactions with circulating albumin (12,13). The bound form (the dominant species, with a Ͼ10-fold signal-enhancing potential) assumes the macromolecular attributes of albumin and remains intravascular, while the nonbound minor component (with the low relaxivity typical of small Gdchelates) is free and extravasates. MP-2269 (Mallinckrodt, Inc., St. Louis, MO) is an experimental monomeric Gd-DTPA-derived blood pool agent with a molecular weight of 1179 g/mol. It is the Gd complex of 4-pentylbicyclo-