The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.

SummaryRust fungi are devastating plant pathogens and cause a large economic impact on wheat production worldwide. To overcome this rapid loss of resistance in varieties, we generated stable transgenic wheat plants expressing short interfering RNAs (siRNAs) targeting potentially vital genes of Puccinia striiformis f. sp. tritici (Pst). Protein kinase A (PKA) has been proved to play important roles in regulating the virulence of phytopathogenic fungi. PsCPK1, a PKA catalytic subunit gene from Pst, is highly induced at the early infection stage of Pst. The instantaneous silencing of PsCPK1 by barley stripe mosaic virus (BSMV)‐mediated host‐induced gene silencing (HIGS) results in a significant reduction in the length of infection hyphae and disease phenotype. These results indicate that PsCPK1 is an important pathogenicity factor by regulating Pst growth and development. Two transgenic lines expressing the RNA interference (RNAi) construct in a normally susceptible wheat cultivar displayed high levels of stable and consistent resistance to Pst throughout the T3 to T4 generations. The presence of the interfering RNAs in transgenic wheat plants was confirmed by northern blotting, and these RNAs were found to efficiently down‐regulate PsCPK1 expression in wheat. This study addresses important aspects for the development of fungal‐derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control cereal rust diseases.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), poses a tremendous threat to the production of wheat worldwide. The molecular mechanisms of Pst effectors that regulate wheat immunity are poorly understood.In this study, we identified an effector Pst18363 from Pst that suppresses plant cell death in Nicotiana benthamiana and in wheat. Knocking down Pst18363 expression by virus-mediated host-induced gene silencing significantly decreased the number of rust pustules, indicating that Pst18363 functions as an important pathogenicity factor in Pst.Pst18363 was proven to interact with wheat Nudix hydrolase 23 TaNUDX23. In wheat, silencing of TaNUDX23 by virus-induced gene silencing increased reactive oxygen species (ROS) accumulation induced by the avirulent Pst race CYR23, whereas overexpression of TaNUDX23 suppressed ROS accumulation induced by flg22 in Arabidopsis. In addition, TaNUDX23 suppressed Pst candidate effector Pst322-trigged cell death by decreasing ROS accumulation in N. benthamiana. Knocking down of TaNUDX23 expression attenuated Pst infection, indicating that TaNUDX23 is a negative regulator of defence. In N. benthamiana, Pst18363 stabilises TaNUDX23.Overall, our data suggest that Pst18363 stabilises TaNUDX23, which suppresses ROS accumulation to facilitate Pst infection.

RNA interference (RNAi) is a powerful genetic tool to accelerate research in plant biotechnology and control biotic stresses by manipulating target gene expression. However, the potential of RNAi in wheat to efficiently and durably control the devastating stripe rust fungus f. sp. () remained largely under explored so far. To address this issue, we generated transgenic wheat () lines expressing dsRNA targeting transcripts of We analyzed expression of and related genes, and resistance traits of the transgenic wheat lines. We show that is an important pathogenicity factor that regulates infection and development of A RNAi construct stably expressed in two independent transgenic wheat lines confers strong resistance to hyphal development is strongly restricted, and necrosis of plant cells in resistance responses was significantly induced. We conclude that trafficking of RNA molecules from wheat plants to may lead to a complex molecular dialogue between wheat and the rust pathogen. Moreover, we confirm the RNAi-based crop protection approaches can be used, to our knowledge, as a novel control strategy against rust pathogens in wheat.

After years of setback, cancer immunotherapy has begun to yield clinical dividends, which are changing the treatment landscape and offering cancer patients the potential for long-term survival, reduced treatment-related toxicity and improved quality-of-life. Using the immune system to treat cancer is known as 'Immuno-oncology' (IO) and agents are sub-classified by their ability to enhance anti-tumor response or to direct the immune system to attack cancer cells via tumor-associated antigens. Areas covered: Clinical trials have demonstrated the effectiveness of several IO agents in many disease sites such as early and advanced stage melanoma, advanced non-small cell lung cancer, bladder, head and neck, gastric, kidney as well as Hodgkin's lymphoma. Notwithstanding the therapeutic excitement generated for patients and clinicians alike, an important consideration is treatment cost, which can reach more than $US100,000 per patient annually. The cost of the drugs, coupled with high disease prevalence and the ever-expanding number of indications, means the current cost trajectory is untenable for most healthcare systems to sustain. Expert commentary: In this paper, the approved IO drugs and those in clinical development are reviewed. The issue of cost effectiveness vs. affordability is then addressed and suggestions that facilitate patient access and long-term sustainability are presented.

Domain of unknown function (DUF) proteins constitute a great deal of families of functionally uncharacterized proteins in eukaryotes. The DUF966 gene family is found in monocotyledons, dicotyledons, mosses, and other species. However, little is known about the functions of DUF966 genes in wheat (Triticum aestivum L.). In this study, we identified and characterized the TaDUF966 gene family members in wheat by in silico analysis. A total of 28 TaDUF966 proteins were identified in wheat. Phylogenetic analysis divided these proteins into two groups (Groups I and II). Proteins in each group showed a highly conserved DUF966 domain and conserved motif distribution, implying their functional conservation. Analysis of gene expression profiling data showed that some TaDUF966 genes were induced by salt stress. We further confirmed the role of TaDUF966-9B in salt stress using virus induced gene silencing (VIGS) assay. Compared with the empty vector control, the TaDUF966-9B knockdown plants exhibited severe leaf curling at 10 days post-inoculation with BSMV under salt stress, suggesting that TaDUF966 genes play a vital role in salt stress tolerance in wheat. Taken together, these results expand our knowledge of the evolution of the DUF966 gene family in wheat and promote the potential application of these genes in wheat genetic improvement.

This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

In many eukaryotes, transcription factor MCM1 gene plays crucial roles in regulating mating processes and pathogenesis by interacting with other co-factors. However, little is known about the role of MCM1 in rust fungi. Here, we identified two MCM1 orthologs, PstMCM1-1 and PstMCM1-2, in the stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst). Sequence analysis indicated that both PstMCM1-1 and PstMCM1-2 contain conserved MADS domains and that PstMCM1-1 belongs to a group of SRF-like proteins that are evolutionarily specific to rust fungi. Yeast two-hybrid assays indicated that PstMCM1-1 interacts with transcription factors PstSTE12 and PstbE1. PstMCM1-1 was found to be highly induced during early infection stages in wheat and during pycniospore formation on the alternate host barberry (Berberis shensiana). PstMCM1-1 could complement the lethal phenotype and mating defects in a mcm1 mutant of Saccharomyces cerevisiae. In addition, it partially complemented the defects in appressorium formation and plant infection in a Magnaporthe oryzae Momcm1 mutant. Knock down of PstMCM1-1 resulted in a significant reduction of hyphal extension and haustorium formation and the virulence of Pst on wheat. Our results suggest that PstMCM1-1 plays important roles in the regulation of mating and pathogenesis of Pst most likely by interacting with co-factors.