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Aberrant expression of fucose or sialic acid containing glycans is prevalent in various cancers, including breast cancer. The addition of fucose and sialic acid to glycans is mediated by fucosyl transferases (FUTs) and sialyl transferases (STs), respectively. To explore the roles of these FUTs and STs in breast cancer, we collected 123 paired breast cancer specimens (tumor tissue and non-tumor tissue) and determined the RNA expression levels of 13 FUTs (FUT1-13) and 13 STs (ST3Gal1-6, ST6Gal1, ST6GalNAc1-4, ST6GalNAc6, ST8Sia1 and ST8Sia4) by q-PCR. The expression of 10 FUTs and 10 STs is significantly higher in tumor tissue than in non-tumor tissue by 1.2-4.09 folds. Notably, expression of FUT1 and ST3Gal1 appeared to be highest in triple negative subtype. Further multivariate Cox regression analysis showed a significant correlation between higher hazard ratios (HRs) for five-year relapse-free survival (RFS) and higher ST3Gal1 expression (N = 16, HR = 2.54, p = 0.02) or lower ST3Gal3 expression (N = 88, HR = 3.44, p < 0.001). As to the joint effects of high expression of ST3Gal1 and low expression of ST3Gal3 (N = 10) compared with low expression of ST3Gal1 and high expression of ST3Gal3 (N = 82), the HR was 5.5 (95% CI = 2.16-14.02, p = 0.0004) for RFS. The two gene additive model displayed a statistically significant HR of 2.33 for RFS (95% CI = 1.48-3.69, p = 0.0003). These results suggest that FUTs and STs play important roles in tumor progression. Citation Format: Yu AL, Liao K-H, Chang C-H, Lin Y-C, Fan T-C, Hung J-T, Yeo H-L, Lin R-J, Yu J-C. Expression levels of sialyl transfereases and fucosyl transferases in breast cancer and their prognostic significance. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-05.

Polyphenol polymerization (PP) catalyzed by MnO2 is an important pathway in humification processes in soils. Due to a lack of aliphatic carbons, the products of PP are considered to be humic substance-like materials (HQs), which are subject to adsorption by Fe (hydr)oxide upon their formation. However, the effects of the interactions of HQs with Fe (hydr)oxide in humification processes have received less attention. In this study, hydroquinone was reacted with birnessite for 1 d (HQ-1). After the removal of residual birnessite, the filtrates were incubated for another 7 and 20 days and were denoted as HQ-7, and HQ-20, respectively. The spectroscopic analyses of the HQ samples indicated that oxidative polymerization of hydroquinone occurred within 1 d. With an increase in incubation time, the molecular structure of the resultant HQ continued to change and became increasingly similar to that of natural humic acid (HA), even in the absence of birnessite. Upon adsorption of the HQs by Fe (hydr)oxide, changes in the IR absorption band indicated the complexation of HQ carboxyl groups with metal centers on the mineral surfaces. HQ-20 was preferentially adsorbed on the Fe (hydr)oxides because it contained a higher number of carboxyl groups than their counterparts with a smaller molecular weight. In addition, the steric arrangements and the distributions of the adsorption sites on Fe (hydr)oxide, closely matching the structures of larger molecules, may also contribute to the preferential adsorption. This study implies that HQs with a larger molecular size can be accumulated in soils while reacting with Fe (hydr)oxides during their formation, and the association of HQs with aliphatic carbons derived from the Maillard reaction may contribute to humic substance (HS) formation.

Photo-decomposition of sulfamethazine (SMT) involves photolytic and photo-catalytic reactions, which occur simultaneously. The relative contributions of these two reactions to the overall SMT photo-decompositions by TiO2 and the intermediates of SMT photo-decompositions were systematically examined with the effects of TiO2 loading, and the pH and the initial SMT concentrations in the solutions. The apparent rate constants of SMT photo-decomposition reactions, which were well described by the pseudo-first-order kinetic model, ranged from 0.24 to 1.61 h−1. The overall photo-decomposition efficiencies of 0.072 mM SMT were the highest at pH 5.5 with 0.5 g L−1 TiO2 due to the adsorption-induced photocatalytic decomposition of SMT on TiO2. However, the SMT photolysis occurred more rapidly at pH 10. Two reactive species of holes and hydroxyl radicals concurrently participated in the photocatalytic decomposition of SMT, and the latter dominated the oxidative reactions of SMT on TiO2. Eight intermediates of SMT photo-decomposition were determined using LC-MS. Their time-dependent distributions indicated that the photo-decomposition of SMT was triggered by hydroxylation on aniline and dimethylpyrimidinyl moieties, followed by the cleavage of the S–N bond of SMT. Our results illustrated that the intermediates with dimethylpyrimidinyl groups possess strong resistance to photo-decomposition and played a determinant role in the photo-decomposition of SMT.

Humic substances are a major component of soil organic matter that influence the behavior and fate of heavy metals such as Cr(VI), a toxic and carcinogenic element. In the study, a repetitive extraction technique was used to fractionate humic acids (HAs) from a peat soil into three fractions (denoted as F1, F2, and F3), and the relative importance of O-containing aromatic and aliphatic domains in humic substances for scavenging Cr(VI) was addressed at pH 1. Spectroscopic analyses indicated that the concentrations of aromatic C and O-containing functional groups decreased with a progressive extraction as follows: F1 > F2 > F3. Cr(VI) removal by HA proceeded slowly, but it was enhanced when light was applied due to the production of efficient reductants, such as superoxide radical and H2O2, for Cr(VI). Higher aromatic- and O-containing F1 fraction exhibited a greater efficiency for Cr(VI) reduction (with a removal rate of ca. 2.89 mmol g−1 HA under illumination for 3 h). 13C NMR and FTIR spectra further demonstrated that the carboxyl groups were primarily responsible for Cr(VI) reduction. This study implied the mobility and fate of Cr(VI) would be greatly inhibited in the environments containing such organic groups.

Since aberrant glycosylation is a feature of cancer cells, targeting tumor associated carbohydrate antigen (TACA) for cancer immunotherapy is gaining international attention. Globo H, the most prevalent TACA over-expressed in cancers of breast, lung, pancreas, stomach, colon, etc., is a hotly pursued target for cancer vaccine. Both Globo H and its pentasaccharide precursor, Gb5, are expressed in breast cancer stem cells. Notably, Globo H ceramide (GHCer) acts as an immune checkpoint molecule, as reflected by uptake of GHCer shed from cancer cells by tumor infiltrating lymphocytes Addition of GHCer to human PBMC, mouse splenocytes or purified CD4+ T cells inhibited their proliferative response to anti-CD3/CD28, and reduced the secretion of IL-2, IFN-γ and IL-4. GHCer also significantly suppressed the proliferation of splenocytes or CD19+ B cells in response to LPS or LPS + IL4 +CD40 ligand and their production of IgG and IgM, with negligible generation of plasma cells. Ceramide displayed no such inhibitory effects. On the other hand, GHCer failed to raise the number of regulatory T cells, or their expression of FOXP3/CTLA4, nor did it increase apoptosis. Molecularly, GHCer significantly suppressed the Notch1 signaling during activation of human PBMC and murine T and B cells. This was linked to GHCer-induced upregulation of expression of ID3 and itch, leading to ID3-dependent downregulation of Notch1 and itch-mediated Notch1 degradation. Furthermore, GHCer increased the expression of egr2 and egr3 at 2hrs after activation which preceded itch upregulation. These results provide the first evidence for GHCer to facilitate the escape of cancer cells from immune surveillance via down-regulation of Notch1 signaling at transcriptional level by ID3, and protein level by egr2/3 controlled itch expression. In addition, GHCer is also incorporated into endothelial cells, through the absorption of microvesicles shed from tumor cells. In endothelial cells, GHCer addition induces migration, tube formation, and intracellular Ca2+ mobilization in vitro and angiogenesis in vivo. Clinically, Globo H+ breast cancer specimens contained Globo H+ tumor infiltrating lymphocytes, and higher vessel density than Globo-H- tumors. Mechanistic investigations linked its angiogenic effects to its binding to TRAX, GHCer is also incorporated into endothelial cells, enhancing angiogenesis. Clinically, Globo H+ breast cancer specimens contained Globo H+ tumor infiltrating lymphocytes, and higher vessel density than Globo-H- tumors. Mechanistic investigations linked the angiogenic effects of GHCer to its binding to TRAX, with consequent release of PLCb1 from TRAX to trigger Ca2+ mobilization. The binding of GHCer to TRAX was validated by Biacore system with immobilized TRAX protein on sensor chip CM5. At concentrations ranging from 9.77 nM to 5 μM, GHCer binds TRAX with a fast association rate, followed by slow dissociation. The KD of the GHCer binding with TRAX was estimated to be about 4.09 x10-8 M, by fitting the binding curves with BIAevaluation 4.1. On the other hand, galactosyl-ceramide, lactosyl-ceramide or Gb4-ceramide showed negligible binding to TRAX. Preliminary data showed that recombinant C-terminal domain of PLCB1 bound to TRAX and was competed by GHCer in a concentration-dependent manner. Taken together, these data support the notion that GHCer plays triple roles in serving as a cancer antigen (including breast cancer stem cells), as an immune checkpoint and as an angiogenic factor, thereby propelling the ongoing multi-national phase II/III clinical trial of globo H vaccine in breast cancer and ovarian cancer. Citation Format: Yu J, Cheng JY, Wang SH, Tsai YC, Wu JC, Hung JT, Lin J, Yeh KT, Yu AL. Globo H ceramide acts as immune checkpoint and angiogenic factor in tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A20.

This work investigates device performances of an AlGaAs/InGaAs metal-oxide-semiconductor pseudomorphic high electron mobility transistor (MOS-pHEMT) by using ozone water oxidation treatment. Experiment results indicate that the studied MOS-pHEMT has demonstrated superior device characteristics as compared to a conventional pHEMT without oxidation treatment on the same epitaxial structure. The studied MOS (conventional)-pHEMT exhibits improved power-added-efficiency (P.A.E.) of 39.6 (36) %, unity-gain cut-off frequency (f T ) of 19.3 (16.8) GHz, maximum oscillation frequency (f max ) of 30.6 (26.7) GHz, minimum noise figure (NF min ) of 1.21 (1.48) dB, and excellent two-terminal gate-drain breakdown voltage (BV GD ) of − 43.1 (−7.9) V, respectively

Background: Globo H, a hexasaccharide linked to ceramide, is a glycolipid over-expressed on the surface of many common cancers. Although globo H has been identified as a potential target for cancer vaccine and clinical trials of globo H vaccine in breast cancer are ongoing, its role in cancers is unknown. Here we investigated the effects of globo H ceramide (GHCer) on immune functions and the underlying mechanisms involved. Methods: The incorporation of globo H by human peripheral blood mononuclear cells (PBMCs) was evaluated by co-culturing PBMCs with globo H expressing breast cancer cell line, MCF-7, and by immunohistochemical analysis of tumor infiltrating lymphocytes in breast cancer specimens. The effects of GHCer on T cells in response to anti-CD3/CD28 activation were assessed by pre-incubation of mouse splenocytes or purified CD4+ T cells or PBMSs with synthetic GHCer. The impacts of GHCer on the mouse CD19+ B cell upon activation with LPS or LPS+IL-4+CD40L were also examined. The effects of GHcer on the protein and gene expression level were determined by flow cytometry and real-time quantitative PCR, respectively. Results: PBMCs co-cultured with MCF-7were found to express GHCer as detected by flow cytometry. Importantly, among 98 breast cancer specimens examined, globo H was detected on tumor-infiltrating lymphocytes in 61% of 61 globo H positive breast cancers. Addition of GHCer to human PBMCs, mouse splenocytes or purified CD4+ T cells inhibited their proliferative response to anti-CD3/CD28 to 60±1%, 50±7% and 62±5% of control, respectively, and significantly reduced the secretion of IL-2, IFN-g and IL-4. GHCer also suppressed the proliferation of splenocytes or purified CD19+ B cells to 45±10% and 26±3% of control in response to LPS or LPS + IL4 +CD40 ligand and reduced their IgM and IgG production, along with negligible induction of plasma cells. Ceramide displayed no such inhibitory effects. On the other hand, GHCer failed to raise regulatory T cells, or their expression of FOXP3/CTLA4, nor did it increase apoptosis. Notably, GHCer significantly suppressed the Notch1 signaling during activation of human PBMC and murine T and B cells. Furthermore, GHCer upregulated the expression of ID3 and itch by 2.1±0.2 and 4.7±0.4 fold, respectively, leading to ID3-dependent downregulation of Notch1 transcription and itch-mediated Notch1 degradation. The latter was associated with increased expression of egr2 and egr3, preceding itch upregulation. Conclusions: Our study uncovered a new aspect of immunosuppressive effects of GHCer which facilitates the escape of cancer from immune surveillance. We also elucidated its molecular processes involving impaired Notch1 signaling through transcriptional repression by ID3, and protein degradation via egr2/3 controlled itch expression. Together with our previous report of the expression of globo H in breast cancer stem cells, these data indicate that GHCer is not merely a cancer-associated antigen, but also acts as an immune checkpoint. Such dual role of GHCer provides further impetus for the development of globo H-targeted cancer immunotherapy and strengthened the rationales for our ongoing phase II/III clinical trial of globo H vaccine in breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-14.

Hemodialysis therapy and the aging process have been reported to interfere with the trace element (TE) status in the body. This multicenter collaborative study on blood levels of TE in geriatric hemodialysis (HD) patients was carried out with an aim to clarify the impact of the aging process and HD therapy on the TE status in such patients.One hundred and fifty-one HD patients (65 male, 86 female), all aged over 60 (68.2+/-3.86 y), and 112 elderly controls (58 male, 54 female) with a mean age of 67.5+/-3.03 were enrolled. All patients underwent standard HD for at least 6 months. The artificial kidneys used were hollow-fiber dialyzers of cellulose membranes. Water used for HD was prepared by reverse osmosis. Blood was collected in the morning prior to dialysis and after fasting. Atomic absorption spectrophotometry was applied to measure blood levels of Pb, Cd and Hg as well as plasma levels of Cu, Zn and Al. Data are presented as mean +/- SEM. Student's t-test and linear regression were applied for statistics.Our geriatric chronic HD patients showed a marked elevation of blood Al and decreased plasma Zn concentrations. The blood levels of Cu, Cd, Pb and Hg were within normal limits. The blood concentrations of Al, Cu and Pb were significantly higher in HD patients than in the normal elderly controls, whereas Cd and Hg were similar in both groups, and Zn were lower in HD patients. Plasma Zn value decreased as dialysis duration increased, however there was a reversely linear correlation between plasma Zn and age.This data reported can be regarded as a starting point and may serve as an insight to further studies on TE imbalances in geriatric and chronic HD populations.

Introduction Hemodialysis therapy and the aging process bave been reported to interfere with the trace element (TE) status in the body. This multicenter collaborative study on blood levels of TE in geriatric hemodialysis (HD) patients was carried out with an aim to clarify the impact of the aging process and HD therapy on the TE status in such patients. Methods One hundred and fifty-one HD patients (65 male, 86 female), all aged over 60 (68.2±3.86 y), and 112 elderly controls (58 male, 54 female) with a mean age of 67.5±3.03 were enrolled. All patients underwent standard HD for at least 6 months. The artificial kidneys used were hollow-fiber dialyzers of cellulose membranes. Water used for HD was prepared by reverse osmosis. Blood was collected in the morning prior to dialysis and after fasting. Atomic absorption spectrophotometry was applied to measure blood levels of Pb, Cd and Hg as well as plasma levels of Cu, Zn and Al. Data are presented as mean ± SEM. Student's t-test and linear regression were applied for statistics. Results Our geriatric chronic HD patients showed a marked elevation of blood Al and decreased plasma Zn concentrations. The blood levels of Cu, Cd, Pb and Hg were within normal limits. The blood concentrations of Al, Cu and Pb were significantly higher in HD patients than in the normal elderly controls, whereas Cd and Hg were similar in both groups, and Zn were lower in HD patients. Plasma Zn value decreased as dialysis duration increased, however there was a reversely linear correlation between plasma Zn and age. Conclusions This data reported can be regarded as a starting point and may serve as an insight to further studies on TE imbalances in geriatric and chronic HD populations.