Search

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs. [ABSTRACT FROM AUTHOR]

In this study, an ordered mesoporous carbon (OMC) was synthesized and investigated as electrodes for capacitive deionization (CDI). The influence of working parameters on salt removal was studied and the electrosorption isotherm and kinetics were investigated. It was found that the electrosorption process fitted both Langmuir isotherm and Freundlich isotherm, and followed pseudo-first-order kinetics. The maximum electrosorptive capacity was 10.1 mg/g at the optimized applied voltage of 1.2V and flow rate of 40 ml/min. In order to investigate the effect of surface groups on CDI efficiency, OMC was modified by H2O2 solution or thermal treatment under N2 atmosphere, without significantly changing its textural properties. X-ray photoelectron spectroscopy measurements showed that the amount of surface oxygen-containing groups was decreased and increased by the thermal and chemical treatments, respectively. CDI experiments revealed that OMC modified by H2O2 solution performed better than original OMC, while thermal treatment worsened the performance of OMC, probably due to the difference in their surface groups. This indicated that the CDI performance of OMC was greatly affected by the surface chemistry. [ABSTRACT FROM AUTHOR]

A 1-dodecanethiol-based phase-transfer protocol is developed for the extraction of noble metal ions from aqueous solution to a hydrocarbon phase, which calls for first mixing the aqueous metal ion solution with an ethanolic solution of 1-dodecanethiol, and then extracting the coordination compounds formed between noble metal ions and 1-dodecanethiol into a non-polar organic solvent. A number of characterization techniques, including inductively coupled plasma atomic emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis demonstrate that this protocol could be applied to extract a wide variety of noble metal ions from water to dichloromethane with an efficiency of > 96%, and has high selectivity for the separation of the noble metal ions from other transition metals. It is therefore an attractive alternative for the extraction of noble metals from water, soil, or waste printed circuit boards. [ABSTRACT FROM AUTHOR]

Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland of irradiated mice successfully restored saliva secretion and increased the number of functional acini. Gene-expression analysis revealed that glial cell line-derived neurotrophic factor (Gdnf) is highly expressed in Lin-CD24+ c-Kit+Sca1+ stem cells. Furthermore, GDNF expression was upregulated upon radiation therapy in submandibular glands of both mice and humans. Administration of GDNF improved saliva production and enriched the number of functional acini in submandibular glands of irradiated animals and enhanced salisphere formation in cultured salivary stem cells, but did not accelerate growth of head and neck cancer cells. These data indicate that modulation of the GDNF pathway may have potential therapeutic benefit for management of radiation-induced xerostomia. [ABSTRACT FROM AUTHOR]

Galectin-1 (Gal-1), a carbohydrate-binding protein whose secretion is enhanced by hypoxia, promotes tumor aggressiveness by promoting angiogenesis and T-cell apoptosis. However, the importance of tumor versus host Gal-1 in tumor progression is undefined. Here we offer evidence that implicates tumor Gal-1 and its modulation of T-cell immunity in progression. Comparing Gal-1--deficient mice as hosts for Lewis lung carcinoma cells where Gal-1 levels were preserved or knocked down, we found that tumor Gal-1 was more critical than host Gal-1 in promoting tumor growth and spontaneous metastasis. Enhanced growth and metastasis associated with Gal-1 related to its immunomodulatory function, insofar as the benefits of Gal-1 expression to Lewis lung carcinoma growth were abolished in immunodeficient mice. In contrast, angiogenesis, as assessed by microvessel density count, was similar between tumors with divergent Gal-1 levels when examined at a comparable size. Our findings establish that tumor rather than host Gal-1 is responsible for mediating tumor progression through intratumoral immunomodulation, with broad implications in developing novel targeting strategies for Gal-1 in cancer. Cancer Res; 71(13); 4423-31. ©2011 AACR. [ABSTRACT FROM AUTHOR]

Ozonation of oxalate in aqueous phase was performed with a commercial activated carbon (AC) in this work. The effect of AC dosage and solution pH on the contribution of hydroxyl radicals (HO·) in bulk solution and oxidation on the AC surface to the removal of oxalate was studied. We found that the removal of oxalate was reduced by tert-butyl alcohol (tBA) with low dosages of AC, while it was hardly affected by tBA when the AC dosage was greater than 0.3 g/L. tBA also inhibited ozone decomposition when the AC dosage was no more than 0.05 g/L, but it did not work when the AC dosage was no less than 0.1 g/L. These observations indicate that HO· in bulk solution and oxidation on the AC surface both contribute to the removal of oxalate. HO· oxidation in bulk solution is significant when the dosage of AC is low, whereas surface oxidation is dominant when the dosage of AC is high. The oxalate removal decreased with increasing pH of the solution with an AC dosage of 0.5 g/L. The degradation of oxalate occurs mainly through surface oxidation in acid and neutral solution, but through HO· oxidation in basic bulk solution. A mechanism involving both HO· oxidation in bulk solution and surface oxidation was proposed for AC enhanced ozonation of oxalate. [ABSTRACT FROM AUTHOR]

Examines the role of genetic and epigenetic control in the spatial and temporal regulation of plant development. Disruption of Arabidopsis histone deacetylase 1 (AtHD1) expression; Role of histone acetylation and deacetylation in plant gene regulation; Use of scanning electron microscopy; Nucleic acid preparation and analysis; Isolation of a stable antisense AtHD1 transgenic plant.