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Murine studies have shown that immunological targeting of fibroblast activation protein (FAP) can elicit protective immunity in the absence of significant pathology. Fibroblast activation protein is a product overexpressed by tumor-associated fibroblasts (TAF) and is the predominant component of the stoma in most types of cancer. Tumor-associated fibroblasts differ from normal adult tissue fibroblasts, and instead resemble transient fetal and wound healing-associated fibroblasts. Tumor-associated fibroblasts are critical regulators of tumorigenesis, but differ from tumor cells by being more genetically stable. Therefore, in comparison to tumor cells, TAF may represent more viable therapeutic targets for cancer immunotherapy. To specifically target TAF, we constructed a DNA vaccine directed against FAP. This vaccine significantly suppressed primary tumor and pulmonary metastases primarily through CD8 + T-cell-mediated killing in tumor-bearing mice. Most importantly, tumor-bearing mice vaccinated against FAP exhibited a 1.5-fold increase in lifespan and no significant pathology. These results suggest that FAP, a product preferentially expressed by TAF, could function as an effective tumor rejection antigen. (Cancer Sci 2010; 101: 2325-2332 T he long-term benefits of immunotherapy in cancer patients are threatened by the escape of tumor cells from the immune system due to the inherent genetic instability of tumor cells.(1) For example, mutations in tumor-specific antigens and downregulation of MHC class I antigen can lead to escape from immune surveillance.(2-4) Additionally, defects in apoptotic signaling pathways or upregulation of apoptosis inhibitors can confer resistance to T-cell-mediated killing.(5) Therefore, to increase the efficacy of cancer immunotherapy, targeting of more genetically stable cells in the tumor stroma may prove beneficial.(5-7)The crucial role of the tumor stroma in tumorigenesis and invasion is becoming more widely recognized.(8-10) Early studies revealed that stromal cells can stimulate the transformation of normal epithelial cells and can produce growth factors, cytokines and chemokines that induce the selection and expansion of neoplastic cells. (8,9) In support of this role, tumor cells inoculated in suspension are less tumorigenic than fragments of solid tumors containing the stroma.(11) Importantly, recent reports have suggested that modulation of tumor-stromal fibroblasts (12) or disturbance of the tumor-stromal network can lead to tumor rejection. (13,14) Tumor-associated macrophages and fibroblasts appear to contribute to the local immunosuppressive microenvironment. (15)(16)(17)(18) Tumor-associated fibroblasts (TAF) synthesize both collagen type I and fibroblast activation protein (FAP), a type II membrane-bound serine protease that exhibits dipeptidyl peptidase and collagenase activities implicated in extracellular matrix remodeling. (7,19,20) Some reports have indicated that overexpression of FAP leads to promotion of tumor growth.Consistently, high levels of stromal FAP ha...

A label-free and sensitive fluorescence method for recognition of sequence-specific DNA using DNA-intercalating dye and metal-organic frameworks (MOFs) is developed. Here, MIL-101 (Cr3F(H2O)2O[(O2C)-C6H4-(CO2)]3·nH2O) is introduced as a quenching platform to decrease the high background fluorescence of SYBR Green I (SG)/probe DNA complex. Mechanism investigations show that MIL-101 can strongly adsorb the SG/probe DNA complex through π-π stacking and electrostatic interactions, and as a consequence, the fluorescence of the SG dye is greatly quenched. While in the presence of target DNA, the as-formed rigid double-stranded (ds) structure of DNA will be far away from the surface of MIL-101; meanwhile, the SG dye can be bound with the dsDNA in the mode of intercalation and minor groove binding, resulting in enhancement of the SG dye fluorescence. The increased signal-to-background ratio has a linear relationship with the concentration of target DNA in the range of 0.1-14 nM. It is confirmed that the detection limit is 73 pM (3σ), which is much lower than that based on the carbon nanotubes and graphene oxide platform. Moreover, one-base-mismatched target DNA can be discriminated effectively. With the introduction of MIL-101, the signal-to-background ratio has been improved ∼8-fold, demonstrating that MIL-101 is an efficient low-background signal platform.

A one-step synthesis of water soluble and pH-responsive trypsin-stabilized fluorescent copper nanoclusters (CuNCs) was reported without using additional protective or reducing agents, and the as-prepared CuNCs exhibited highly stable properties including oxidation resistance, thermal stability and photostability.

Cataract blindness control is well underway in rural China, as evidenced by significant increases in cataract surgical coverage and improvement in visual acuity outcomes during the 2006-2014 interval. Further efforts are needed to provide greater access to affordable cataract surgery for the elderly, female persons, and those with little or no education.

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We investigate 239 firms cited in the SEC's Accounting and Auditing Enforcement Releases (AAERs). We document significantly negative abnormal operating performance (measured using both cash-flow-based and earnings-based metrics) in the second and third years following AAERs. We also detect significantly negative abnormal stock returns in up to three years following AAERs. We further find that AAER firms are more likely to fail in the post-AAER period. Taken together, our findings suggest that the negative implications of an AAER citation resulting from egregious financial reporting violations can be long lasting and influence various facets of firm performance and survivability.