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Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer, CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.

Currently, vaccine is a promising tumor prevention modality in cancer therapy. However, it is hard to elicit robust antitumor immunity in patients already afflicted with tumor, inspiring a need for a firenew and subversive cancer therapeutic vaccine. Herein, we reported an in situ STING (stimulator of interferon genes)-activating vaccination (ISSAV) strategy to completely convert primary tumor towards an in situ therapeutic STING vaccine for initiating highly effective and personalized antitumor immune responses. This ISSAV strategy represented a broad-spectrum cancer therapeutic vaccine, which break the shackles of heterogeneity and immunosuppression. We developed an ideational ingenious biomimetic nanoplatform (CMM-DiR) for achieving ISSAV strategy, which encapsulated STING-agonist (MnO2 NPs) and immobilized photothermal agent (DiR). In the tumor microenvironment (TME), CMM-DiR realized burst release of Mn2+, increased the pH value of TME, alleviated tumor hypoxia and induced the expose of numerous tumor-associated antigens from cancer cells. Accordingly, the primary tumor had the dual-function of as adequate antigens and STING agonist depots, thus transforming into a therapeutic STING vaccine. Importantly, the robust antitumor immunity of nanoplatform was observed in primary tumor, recurrent tumor, metastatic tumor and multinodular tumor, demonstrating that this ISSAV represents a technological advancement in the field of cancer vaccinations and personalized immunotherapy.

High temperatures seriously limit plant growth and productivity. Investigating heat-responsive molecular mechanisms is important for breeding heat-tolerant crops. In this study, heat-responsive mechanisms in leaves from a heat-sensitive spinach (Spinacia oleracea L.) variety Sp73 were investigated using two-dimensional gel electrophoresis (2DE)-based and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics approaches. In total, 257 heat-responsive proteins were identified in the spinach leaves. The abundance patterns of these proteins indicated that the photosynthesis process was inhibited, reactive oxygen species (ROS) scavenging pathways were initiated, and protein synthesis and turnover, carbohydrate and amino acid metabolism were promoted in the spinach Sp73 in response to high temperature. By comparing this with our previous results in the heat-tolerant spinach variety Sp75, we found that heat inhibited photosynthesis, as well as heat-enhanced ROS scavenging, stress defense pathways, carbohydrate and energy metabolism, and protein folding and turnover constituting a conservative strategy for spinach in response to heat stress. However, the heat-decreased biosynthesis of chlorophyll and carotenoid as well as soluble sugar content in the variety Sp73 was quite different from that in the variety Sp75, leading to a lower capability for photosynthetic adaptation and osmotic homeostasis in Sp73 under heat stress. Moreover, the heat-reduced activities of SOD and other heat-activated antioxidant enzymes in the heat-sensitive variety Sp73 were also different from the heat-tolerant variety Sp75, implying that the ROS scavenging strategy is critical for heat tolerance.

M O N D A Y 689 Oral Allergy Syndrome a Spectrum Of Presentations Dr. Parwinder Gill, Dr. Gordon L. Sussman, FAAAAI, Jiayi Bian, Ms. Carly Barron; University of Toronto, Toronto, ON, Canada, University of Toronto, Faculty of Medicine, Toronto, ON, Canada, Gordon Sussman Clinical Research Inc., Toronto, ON, Canada. RATIONALE:We report a case series of patients presenting with features of oral allergy syndrome (OAS) with clinical symptoms ranging from gastrointestinal upset to anaphylaxis. This highlights the possibility that OASmay present not only as local irritation of the oropharynx, but can also manifest asmore serious symptoms such as gastrointestinal upset, and even anaphylaxis. METHODS: Our report consists of six individuals who presented with gastrointestinal symptoms alone, and four individuals who presented with severe allergic reactions, who underwent allergy testing for investigation. RESULTS: In all ten cases, clinical history in addition to the results of the allergy testing was consistent with oral allergy syndrome presenting as gastrointestinal upset or anaphylaxis in response to their triggers. CONCLUSIONS: OAS is an IgE-mediated allergic reaction resulting from cross-reactivity of pollens, mainly birch and ragweed with certain nuts, fruits and vegetables. This is generally recognised as a benign syndrome presenting as local itching of the mouth occurring after contact with these foods. However, oral allergy syndrome can manifest as gastrointestinal symptoms and even anaphylactic allergy. We report these cases to alert the possibility that oral allergy syndrome can present as a spectrum of symptoms and can result in serious systemic reactions.