FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.

FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer

Library Assessment and Data Analytics in the Big Data Era: Practice and Policies

Emerging technologies have offered libraries and librarians new ways and methods to collect and analyze data in the era of accountability to justify their value and contributions. For example, Gallagher, Bauer and Dollar (2005) analyzed the paper and online journal usage from all possible data sources and discovered that users at the Yale Medical Library preferred the electronic format of articles to the print version. After this discovery, they were able to take necessary steps to adjust their journal subscriptions. Many library professionals advocate such data-driven library management to strengthen and specify library budget proposals

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. RESULTS: Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS: Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis

Outcomes of patients with rodenticide poisoning at a far east poison center

BACKGROUND: Rodenticide poisoning remains a major public health problem in Asian countries. Nevertheless, very few data are available in world literature regarding the outcomes of these patients. Therefore, the purpose of this study was to investigate the clinical outcomes of rodenticide poisonings in our hospital and to compare these data with published reports from other international poison centers. FINDINGS: We retrospectively examined the records of 20 patients with rodenticide poisoning (8 brodifacoum, 12 bromadiolone) who were referred to Chang Gung Memorial Hospital between 2000 and 2011. It was found that most of the rodenticide patients were middle-aged adults. Both genders were equally affected and many patients had a past history of major depressive disorder or schizophrenia. Nevertheless, patients with bromadiolone were referred significantly sooner than patients with brodifacoum poisoning (0.1 ± 0.1 versus 5.5 ± 10.5, P < 0.001). Furthermore, it was found that patients with brodifacoum suffered higher incidences of ecchymosis (50.0% versus 0%, P = 0.006) and hematuria (50.0% versus 0%, P = 0.006) than patients with bromadiolone poisoning. Laboratory analysis also demonstrated a poorer hemostatic profile of patients with brodifacoum [prothrombin time (PT), international normalized ratio (INR), 4.3 ± 4.8 versus 1.0 ± 0.1, P = 0.032; PT prolongation, 50.0% versus 0%, P = 0.006; activated partial thromboplastin time (aPTT) prolongation, 50.0% versus 0%, P = 0.006] than patients with bromadiolone poisoning. At the end of analysis, no patient died of the poisoning. CONCLUSION: The favorable outcome (zero mortality rate) is comparable to the published reports from other international poison centers. Further studies are warranted

The Assessment for Sensitivity of a NO2 Gas Sensor with ZnGa2O4/ZnO Core-Shell Nanowires—a Novel Approach

The application of novel core-shell nanowires composed of ZnGa2O4/ZnO to improve the sensitivity of NO2 gas sensors is demonstrated in this study. The growth of ZnGa2O4/ZnO core-shell nanowires is performed by reactive evaporation on patterned ZnO:Ga/SiO2/Si templates at 600 °C. This is to form the homogeneous structure of the sensors investigated in this report to assess their sensitivity in terms of NO2 detection. These novel NO2 gas sensors were evaluated at working temperatures of 25 °C and at 250 °C, respectively. The result reveals the ZnGa2O4/ZnO core-shell nanowires present a good linear relationship (R2 > 0.99) between sensitivity and NO2 concentration at both working temperatures. These core-shell nanowire sensors also possess the highest response (<90 s) and recovery (<120 s) values with greater repeatability seen for NO2 sensors at room temperature, unlike traditional sensors that only work effectively at much higher temperatures. The data in this study indicates the newly-developed ZnGa2O4/ZnO core-shell nanowire based sensors are highly promising for industrial applications