Glioblastomas belong to the most aggressive human cancers with short survival times. Due to the blood-brain barrier, they are mostly inaccessible to traditional chemotherapy. We have recently shown that doxorubicin bound to polysorbate-coated nanoparticles crossed the intact blood-brain barrier, thus reaching therapeutic concentrations in the brain. Here, we investigated the therapeutic potential of this formulation of doxorubicin in vivo using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5-8 glioblastoma-bearing rats (total n ‫؍‬ 151) were subjected to 3 cycles of 1.5-2.5 mg/kg body weight of doxorubicin in different formulations, including doxorubicin bound to polysorbate-coated nanoparticles. The animals were analyzed for survival (% median increase of survival time, Kaplan-Meier). Preliminary histology including immunocytochemistry (glial fibrillary acidic protein, ezrin, proliferation and apoptosis) was also performed. Rats treated with doxorubicin bound to polysorbate-coated nanoparticles had significantly higher survival times compared with all other groups. Over 20% of the animals in this group showed a long-term remission. Preliminary histology confirmed lower tumor sizes and lower values for proliferation and apoptosis in this group. All groups of animals treated with polysorbatecontaining formulations also had a slight inflammatory reaction to the tumor. There was no indication of neurotoxicity. Additionally, binding to nanoparticles may reduce the systemic toxicity of doxorubicin. This study showed that therapy with doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma.

[1] Fluxes of N 2 O, NO, NO 2 , CO 2 , and CH 4 were measured with high temporal resolution for 3 months at a tropical rain forest site in Queensland, Australia, using automated measuring systems. During this period, representing the transition between dry and wet season, huge pulses of NO emissions from the soil exceeding 500 mg N m À2 h À1were observed with the onset of the first rainfalls. . Though a significant amount of the NO emitted from the soil was redeposited to the soil surface after its oxidation to NO 2 (0.7 kg N ha À1 ), the observed magnitude of net NO x release from the soil indicates that NO x emissions from tropical rain forest ecosystems are seriously underestimated. The mean CO 2 emission was 159.0 mg C m À2 h À1 (range: 36.3-284.8 mg C m À2 h À1 ) and thus >2 magnitudes higher than NO emissions. Among the C-and N-trace gases measured, the temporal variability of CH 4 uptake was the lowest. The mean uptake rate for CH 4 was

Mouse gammadelta T cells produce IL-17 in response to lung injury and are required for an organized inflammatory response and epithelial repair. The lack of gammadelta T cells correlates with increased inflammation and fibrosis.

Increased expression of the cell proliferation-associated polo-like kinase 1 (PLK1) and apoptosis-associated BCL-2 genes has been observed in different human malignancies. Inhibition of cell proliferation and reactivation of apoptosis are basic principles in anticancer therapy. The efficiency of this approach is often limited by insuf-ficient targeting and delivery of anticancer drugs into the tumors. Phosphorothioate antisense oligodeoxynucleotides (ODNs) directed against PLK1 and BCL-2 were administered systemically via the tail vein into nude mice bearing A549, MDA-MB-435, and Detroit562 xenografts. To enhance tumor-specific uptake and to reduce systemic toxicity of antisense ODNs membrane electroporation transfer was applied in vivo. Northern and Western blot analyses were used to assess PLK1 and BCL-2 expression. Tumor mass was assessed after resection of tumors. All three cell lines and corresponding xenografts expressed high levels of PLK1 and were sensitive towards antisense PLK1 treatment. Antisense BCL-2 therapy was effective in tumors expressing high levels of BCL-2, but not in A549 cells and corresponding xenografts, which express low levels of BCL-2. Administration of antisense ODNs in a dose of 5 mg/kg, twice weekly during four weeks supported by the membrane electroporation transfer, eradicated 60-100% of the xenografted tumors. Antitumor effect in BCL-2 overexpressing MDA-MB-435 cells was synergistic for BCL-2 and PLK1 combination therapy. This study provides evidence that combined systemic administration of antisense ODNs against proliferation and pro- survival associated targets and in vivo electroporation of tumors represents a promising antitumor therapeutic approach.

Purpose: To establish an estimate for the mean pulmonary arterial pressure (mPAP) derived from noninvasive data acquired with magnetic resonance (MR) velocity-encoded sequences. Materials and Methods:In seven sedated pigs synchronous catheter-based invasive pressure measurements (IPM) and noninvasive MR were acquired in the main pulmonary artery (MPA) at different severities of pulmonary arterial hypertension (PAH) that were caused by infusion of thromboxane A2 (TxA2). The invasively measured mPAP was correlated with the noninvasive MR velocity data and linear combination equations (LCE) were computed. Conclusion:Applying the identified LCE allowed the estimation of the mPAP in an acute and resistance-based model of PAH with high accuracy using noninvasive MR velocity-encoded sequences.