Absolute cross sections for electron-impact detachment and electron-impact dissociation of CN− and BO− were measured for electron energies from threshold to 40 eV. With both ions we see only little dissociation when electron detachment occurs. In the case of CN− a resonance in the detachment cross section is discovered at an energy of ∼10 eV. No resonances were seen in the case of BO−. We argue that the resonance observed for CN− is due to an excited state of the dianion. The nonresonant part of the detachment cross section is found to follow the classical prediction given by Andersen et al. [Phys. Rev. Lett. 74, 892 (1995)].

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Larger NMR magnets with relatively high field strengths have become available recently, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. The aim of this study was to develop and test a new and simple kidney perfusion model from slaughterhouse swine using a new 4.7-tesla/40-cm diameter system, with the intention behind to provide a human-like mammalian experimental kidney perfusion model, and to avoid sensitive in vivo animal experiments on higher-developed mammalians. 35 pig kidneys obtained 10–15 min post mortem were studied to evaluate and define conditions for optimum metabolic preservation with the following perfusion protocols: (1) immediate plegia with cold Collins solution, 1–3 h cold storage, P-31 MRS; (2) immediate plegia, 1–3 h cold storage, blood reperfusion, P-31 MRS; (3) immediate blood reperfusion, plegia, 1–3 h cold storage, blood reperfusion, P-31 MRS; (4) immediate blood reperfusion, plegia, 24 h cold storage, blood reperfusion, P-31 MRS. P-31 MRS at 81 MHz with a double-tuned surface coil yielded the following results: Protocol, No.

iNKT cells – often referred as the “Swiss Army knife” of the immune system ‒ have emerged as central players in cancer vaccine therapies. Glycolipids activating iNKT cells, such as α-galactosylceramide (αGalCer), can enhance the immune response against co-delivered cancer antigens and have been applied in the design of self-adjuvanting anti-tumor vaccines. In this context, this work focuses on the chemical synthesis of ganglioside tumor-associated carbohydrate antigens (TACAs), namely GM3 and (Neu5Gc)GM3 antigens, their conjugation to αGalCer, and their formulation into liposomes as an efficient platform for their in vivo delivery. Liposomes containing GM3‒αGalCer, (Neu5Gc)GM3‒αGalCer, and equimolar amounts of the two conjugates have been fully characterized and their ability to activate iNKT cell has been confirmed in vitro. Finally, the candidates were tested in in vivo immunization studies, demonstrating an ability to induce both Th1 and Th2 cytokines further leading to the production of all subclasses of IgG antibodies. Notably, the study also demonstrated that serum antibodies raised against the two TACAs alone and in combination were cross-reactive. This finding has consequences for future vaccine designs – even if a highly tumor-selective antigen is chosen, the resulting antibody response may be broader than anticipated.

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The lack of tumor-specific targets that allow for selective eradication of malignant cells without affecting healthy tissues is a major drawback of cancer chemotherapy. In contrast to normal cells, tumor cells frequently contain multiple centrosomes, associated with the formation of multipolar mitotic spindles and chromosome segregation defects. In many tumor types, mitotic stability is regained after clonal selection by coalescence of multiple centrosomes into two functional spindle poles (centrosomal clustering). To identify potent and selective inhibitors of centrosomal clustering, we recently described a phenotype-based small molecule screening strategy directed to induce tumor cells with supernumerary centrosomes to undergo multipolar mitoses, thereby resulting in apoptotic cell death (Rebacz et al., Cancer Res2007; 67: 6342–6350). We here describe the novel small molecule GF-15, which is a derivative of griseofulvin and a potent inhibitor of centrosomal clustering, thereby inducing multipolar spindles followed by apoptosis. We tested more than 25 cancer cell lines from hematologic malignancies (including acute and chronic leukemias, lymphomas and multiple myeloma) as well as solid tumors (including glioblastoma, colon, cervix, and pancreatic cancers) and found mean inhibitory concentrations (IC50) for proliferation and survival in the range of 1–5μM GF-15, associated with activation of caspases 8, 9, and 3. As expected, tumor cell lines displaying only limited centrosomal aberrations or microsatellite instability were less sensitive to treatment with GF-15. Importantly, non-malignant cells without supernumerary centrosomes including PBMCs, immortalized hepatocytes, and bone marrow stromal cells, did not reach their IC50 even at 30μM GF-15. Specifically, cell cycle analysis of synchronized tumor cells showed marked G2/M arrest, followed by a dramatic increase of the sub-G1 fraction, after treatment with GF-15. In addition, short term treatment with GF-15 was also associated with inhibition of cytokine-triggered cell migration. Finally, both intraperitoneal and oral GF-15 treatment of murine xenograft models of human colon cancer and multiple myeloma resulted in tumor growth inhibition and significantly prolonged survival in vivo. Taken together, our results demonstrate the in vitro and in vivo anti-tumor efficacy of a first in class small molecule inhibitor of centrosomal clustering with specificity for tumor cells, and strongly support its clinical evaluation to improve patient outcome in both hematologic malignancies and solid tumors.

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