Recent changes of trans-boundary air pollution over the Yellow Sea: Implications for future air quality in South Korea.

The influence of air pollutants originating from the Chinese region on air quality over South Korea has been a major concern for policymakers. To investigate the inter-annual trends of the long-distance transport of air pollutants from China to South Korea, multi-year trend analysis was carried out for Aerosol Optical Depth (AOD, as a proxy of particulate matter), and CO (a water-insoluble air pollutant) and SO2 (a partially water-soluble air pollutant), over three regions in Northeast Asia. Air pollutants are typically long-range transported from the highly polluted parts of China to South Korea through the Yellow Sea. Taking advantage of this geographical merit, we carried out the multi-year trend analysis with a special focus on the Yellow Sea region. Decreasing trends of about 5-10%, 13-17% and 55-61% during the last decade were observed in surface CO, AOD and tropospheric SO2 columns over the North China Plain (NCP), Yellow Sea (YS), and South Korea (SK), respectively. Such decreasing trends were also found consistently during the last three, five, and seven years, indicating that the changes in pollution levels are likely in response to recent policy measures taken by the Chinese and Korean governments to improve air quality over the regions. Due to these efforts, the amounts of air pollutants transported from China to South Korea are expected to decrease in future years, to the likely rates of 1.50 ppb yr-1, 0.05 DU yr-1, and 0.56 µg m-3 yr-1 over the YS region for CO, SO2, and PM2.5, respectively. Given the ambitious plans recently announced by the Chinese government for the 21st meeting of Conference of Parties (COP21) and its co-control effects, the suggested percentage rates may even be conservative numbers. This analysis is expected to provide South Korean policymakers with valuable information to establish new air pollution policies in South Korea.

Tumor endothelial marker 8 promotes cancer progression and metastasis.

Every year more than 8 million people suffer from cancer-related deaths worldwide [1]. Metastasis, the spread of cancer to distant sites, accounts for 90% of these deaths. A promising target for blocking tumor progression, without causing severe side effects [2], is Tumor Endothelial Marker 8 (TEM8), an integrin-like cell surface protein expressed predominantly in the tumor endothelium and in cancer cells [3, 4]. Here, we have investigated the role of TEM8 in cancer progression, angiogenesis and metastasis in invasive breast cancer, and validated the main findings and important results in colorectal cancer. We show that the loss of TEM8 in cancer cells results in inhibition of cancer progression, reduction in tumor angiogenesis and reduced metastatic burden in breast cancer mouse models. Furthermore, we show that TEM8 regulates cancer progression by affecting the expression levels of cell cycle-related genes. Taken together, our findings may have broad clinical and therapeutic potential for breast and colorectal primary tumor and metastasis treatment by targeting TEM8.

Correction: Inferring Protein Modulation from Gene Expression Data Using Conditional Mutual Information.

[This corrects the article DOI: 10.1371/journal.pone.0109569.].

Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma.

Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 µg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.

Inferring protein modulation from gene expression data using conditional mutual information.

Systematic, high-throughput dissection of causal post-translational regulatory dependencies, on a genome wide basis, is still one of the great challenges of biology. Due to its complexity, however, only a handful of computational algorithms have been developed for this task. Here we present CINDy (Conditional Inference of Network Dynamics), a novel algorithm for the genome-wide, context specific inference of regulatory dependencies between signaling protein and transcription factor activity, from gene expression data. The algorithm uses a novel adaptive partitioning methodology to accurately estimate the full Condition Mutual Information (CMI) between a transcription factor and its targets, given the expression of a signaling protein. We show that CMI analysis is optimally suited to dissecting post-translational dependencies. Indeed, when tested against a gold standard dataset of experimentally validated protein-protein interactions in signal transduction networks, CINDy significantly outperforms previous methods, both in terms of sensitivity and precision.

Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients.

This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy derived from plasmacytoid dendritic cells that typically involves the skin and rapidly progresses to a leukemia phase. Despite being initially responsive to intensive combination chemotherapy, most patients relapse and succumb to their disease. Because BPDCN blasts overexpress the interleukin-3 receptor (IL3R), the activity of SL-401, diptheria toxin (DT)388IL3 composed of the catalytic and translocation domains of DT fused to IL3, was evaluated in BPDCN patients in a phase 1-2 study. Eleven patients were treated with a single course of SL-401 at 12.5 µg/kg intravenously over 15 minutes daily for up to 5 doses; 3 patients who had initial responses to SL-401 received a second course in relapse. The most common adverse events including fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia were transient. Seven of 9 evaluable (78%) BPDCN patients had major responses including 5 complete responses and 2 partial responses after a single course of SL-401. The median duration of responses was 5 months (range, 1-20+ months). Further studies of SL-401 in BPDCN including those involving multiple sequential courses, alternate schedules, and combinations with other therapeutics are warranted. This trial is registered at clinicaltrials.gov as #NCT00397579.