tbuckley/cabot-search huggingface dataset:
Abstract 1481: Srx-Prx IV axis is required for human lung cancer cell maintenance, migration, and invasion
Authors: Qiou Wei, Hong Jiang, Zhen Xiao, Andrew Stephen, Alyson Baker, Matthew R. Young, Timothy D. Veenstra, Nancy H. Colburn
Journal: Cancer Research (2010)

Abstract Sulfiredoxin (Srx) is a novel antioxidant protein that has been shown to reduce the hyper oxidized Peroxiredoxins (Prxs). Our previous study has demonstrated that Srx is required for tumor promoter induced cell transformation and is highly expressed in certain types of human skin cancers (Wei et al PNAS 2008). In this study, our goal is to further examine the expression of Srx in a broad range of human tumors and to explore its functional significance and molecular mechanisms in human cancer development. We found that Srx is highly expressed in several types of human lung cancers and its level is correlated with cancer malignancy and metastasis. Using human lung cancer A549 cell in culture, we found that knockdown of Srx significantly reduces anchorage independent growth in soft agar, cell migration in a wound-healing assay and cell invasiveness in a matrigel invasion assay. In an effort to discover downstream mediators of Srx-signaling pathway, we used affinity-based pull down and mass spectrometry methods to identify proteins that interact with Srx. To our surprise, Prx IV was found to be the most abundant protein that interacts with Srx in at least three different cell lines and the preferential interaction occurs independently of its expression levels. To characterize the Srx-Prx IV interaction, bacterial expressed recombinant Srx, Prx I, II, III and IV were individually purified. In an in vitro binding assay using Surface Plasmon Resonance technique, we confirmed that purified Srx has a much higher binding affinity to Prx IV than to Prx I, II or III. With a lentiviral based shRNA technology, each individual Prx was specifically knocked down in A549 cells. The phenotypic changes of these cells were compared to the Srx knockdown cells. We found that knockdown of Prx IV, but not other Prxs, was sufficient to recapitulate the attenuation of tumor phenotype and progression of Srx knockdown cells. In addition, we also confirmed that Prx IV undergoes rapid hyperoxidation in the presence of oxidative stress and is preferentially reduced by Srx in A549 cells. Overall our data indicate that Srx is highly expressed in human lung cancers and Srx-Prx IV axis is critical for human lung cancer cell maintenance, migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1481.
Abstract 930: Reprogramming the transcriptional response to hormone through functionally-distinct classes of gene enhancers in prostate cancer cells
Authors: Ivan Garcia-Bassets, Dong Wang, Chris Benner, Li Wenbo, Xue Su, Christopher K. Glass, Michael G. Rosenfeld, Xiang-Dong Fu
Journal: Cancer Research (2011)

Abstract Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, which contribute to the activation of cell-type specific enhancers by selectively favoring the recruitment of key regulated transcription factors such as the androgen receptor (AR) in prostate cancer cells, can simultaneously restrict these same factors from activating additional (alternative) pre-established but yet inactive enhancers, thus licensing specific signal-activated responses and restricting others. Importantly, these alternative hormonal responses are linked to distinct structural and functional classes of enhancers. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in some sets of advanced prostate tumors, causes a massive switch in AR binding from one functional enhancer class to another, which massively reprograms the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated “restriction” of AR binding to the new enhancer class that requires no apparent nucleosome remodeling for their activation. Multiple global analyses of enhancer formation, structure, looping, and activation were combined to support these conclusions, including: H3K4me1/me3, H3K27ac, and H4K4ac mapping (ChIP-seq); nucleosomal H3K4me2 mapping (nucleosomal ChIP-seq); FoxA1, AR, p300, and MED12 mapping (ChIP-seq), also supported by the 3C assay; enhancer ncRNA or eRNAs generation analysis (GRO-seq); and gene expression analysis (microarray and GRO-seq). Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce alternative gene expression programs, which -we speculate- may underlie many sequential gene expression events in development or during cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 930. doi:10.1158/1538-7445.AM2011-930
Underperformance of Gallium-67 Scan is Greater in Relapse Than in Initial Staging, Compared With FDG PET
Authors: Yu-Yi Huang, Dong-Ling You, Mei-Ching Liu, Tran-Der Tan, Pei-Ing Lee, Ming-Yuan Lee
Journal: Clinical Nuclear Medicine (2011)

The purpose of this study is to evaluate the performance of gallium-67 scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and recurrence detection by comparing the 2 imaging studies in the same patient.A total of 42 patients from the period between July 2002 and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG PET scans and also underwent corresponding GS performed within 7 days of FDG PET, for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed in these 42 patients, 27 were for staging, and 19 for restaging after recurrence.In all these studies, FDG PET detected 230 lesion sites, whereas GS detected 85 lesion sites. All of the lesions detected by GS were noted on FDG PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the 27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68 lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110 lesions, whereas GS detected only 17 (15.5%).FDG PET is superior to GS in staging and detecting all types of lymphoma. The difference is notably more significant in recurrence detection.
Prevention of Human Diabetic Ketoacidosis by Somatostatin
Authors: John E. Gerich, Mara Lorenzi, Dennis M. Bier, Victor Schneider, Eva Tsalikian, John H. Karam, Peter H. Forsham
Journal: New England Journal of Medicine (1975)

To evaluate the role of glucagon in the pathogenesis of diabetic ketoacidosis in man, we studied the effect of suppression of glucagon secretion by somatostatin on changes in plasma beta-hydroxybutyrate and glucose concentrations (as well as changes in their precursors) after acute withdrawal of insulin from seven patients with juvenile-type diabetes. Suppression of glucagon secretion prevented the development of ketoacidosis for 18 hours after acute insulin withdrawal, whereas in control studies mild ketoacidosis occurred 10 hours after insulin was stopped. Plasma beta-hydroxybutyrate, glucose, free fatty acid, and glycerol levels were all markedly lower during suppression of glucagon secretion (p smaller than 0.001), whereas plasma alanine levels were higher (p smaller than 0.001). These studies indicate that insulin lack per se does not lead to fulminant diabetic ketoacidosis in man and that glucagon, by means of its gluconeogenic, ketogenic, and lipolytic actions, is a prerequisite to the development of this condition.
TCT-760 Treatment of Acquired von Willebrand Syndrome in Aortic Stenosis with Transcatheter Aortic Valve Replacement (TAVR)
Authors: Tobias Spangenberg, Ulrich Budde, Thielsen Thomas, Christian Frerker, Karl-Heinz Kuck, Ulrich Schäfer
Journal: Journal of the American College of Cardiology (2014)
P179 BINDING OF HEPATITIS B VIRUS TO ITS CELLULAR RECEPTOR ALTERS THE EXPRESSION PROFILE OF GENES OF THE BILE ACID METABOLISM
Authors: N. Oehler, T. Volz, J. Kah, L. Allweiss, K. Giersch, J. Petersen, A.W. Lohse, S. Urban, M. Lutgehetmann, J. Heeren, M. Dandri
Journal: Journal of Hepatology (2014)
Abstract 5454: Androgen-independent regulation of cellular signaling, transcriptional activity, and mRNA stability in a cell model of prostate cancer.
Authors: Suzanne M. Smith, Kay K. Opperman, Barbara J. Kaboord, Peter A. Bell
Journal: Cancer Research (2013)

Abstract Prostate cancer progression relies on the interplay between androgen dependent and independent processes. Depending on the cell type and stimulus, the independent pathway may result in proliferation, progression, or inhibition. It recently has become evident that the molecular mechanisms that drive the differentiation of normal prostate cells towards abnormal proliferation involve multiple signal transduction cascades that often overlap and interact. Through a combination of multiple techniques, including chromatin immunoprecipitation (chIP) and RNA pull-down, we are able to correlate cellular signaling events to androgen receptor transcriptional activity, and how it relates to cancer progression by using growth factors and hormones. In growth factor stimulated LNcap prostate cancer cells, we observed activation of Stat3 and PI3K pathways and reduced transcriptional activity of typical androgen receptor DNA targets, such as prostate-specific antigen (PSA) and cyclin-dependent kinase inhibitor (CDKN1A or p21). However, in estradiol stimulated cells we detected an increase transcriptional activity of the above targets as well as activation of proliferation pathways. Because the androgen receptor and its targets are also regulated by mRNA stability through the UTR, we assessed RNA stability using RNA pull-down assays and RT-PCR. Our results, and those already published, indicate that multiple overlapping signal transduction pathways are involved in the abnormal differentiation of prostate cells; therefore, our use of a combination of tools is advantageous in further defining the model of cancer progression and potential therapies. Citation Format: Suzanne M. Smith, Kay K. Opperman, Barbara J. Kaboord, Peter A. Bell. Androgen-independent regulation of cellular signaling, transcriptional activity, and mRNA stability in a cell model of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5454. doi:10.1158/1538-7445.AM2013-5454
Abstract 1943: A comparison of three techniques to induce efficient <i>ex vivo</i> T-cell expansion
Authors: Chris L. Langsdorf, Jixiang Liu, Jolene Bradford, Gayle Buller
Journal: Cancer Research (2010)

Abstract The current study was undertaken to evaluate three common methods of inducing proliferation in a T lymphocyte population. In the first method cells are treated with purified monoclonal mouse anti-human CD3 antibody followed by addition of interleukin-2. The second approach involves treatment with the mitogen Concanavalin A. The third technique makes use of monoclonal mouse antibodies against human CD3 and CD28 immobilized on the surface of superparamagnetic polystyrene microspheres. Human peripheral blood mononuclear cells were isolated from fresh whole blood using a centrifuge density gradient. Cells were stained with CellTrace™ Violet, a novel cell proliferation tracing dye with a mode of action similar to carboxyfluorescein diacetate succinimidyl ester (CFSE), and resuspended in OpTmizer T-Cell Expansion Buffer (GIBCO) containing L-glutamine, penicillin and streptomycin. Stained cells were treated with one of the three stimulation techniques and incubated at 37°C and 5% CO2 for 7 days. A cell impermeant nucleic acid dye was used to evaluate the effect of each treatment on cell viability. The specific subpopulations induced to proliferate with each treatment were characterized in multicolor flow cytometry using monoclonal antibody conjugates against human CD3, CD4, and CD8. Cells treated with CD3/IL-2 or Concanavalin A showed a moderate, heterogeneous level of stimulation, with some cells undergoing 9 cell divisions, others remaining senescent, and approximately equal amounts remaining in generations 1 through 8. Microsphere-bound antibodies provided a much stronger, more uniform stimulus as evidenced by the very high proliferative index of cells. Concanavalin A treatment was mildly cytotoxic, while viability of cells treated with free or bound antibodies was similar to unstimulated cells. The strong, homogeneous stimulus provided by superparamagnetic polystyrene expansion beads is useful when massive numerical expansion of T lymphocytes is desired for subsequent research or adoptive transfer in vivo, but does not appear to be as useful when a population containing several discrete generations of cells is desired. The more moderate stimuli resulting from treatment with CD3/IL-2 or Concanavalin A result in a less efficient numerical expansion, but provide an excellent tool to evaluate the phenotype and pedigree of cells as they proliferate through several generations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1943.
Abstract 2837: Assay development for the discovery of semaphorin 3B-inducing agents from natural product sources
Authors: Yeonjoong Yong, Li Pan, Yulin Ren, A. Douglas Kinghorn, Steven M. Swanson, Esperanza J. Carcache de Blanco
Journal: Cancer Research (2012)

Abstract The family of semaphorins has been found to regulate cell adhesion and cell motility, the immune response, angiogenesis, and tumor progression. The semaphorins are emerging as regulators of key processes of tumor progression. Semaphorin 3B, in particular, has been found to inhibit proliferation and promote apoptosis. Since there is yet no screening assay available to be used in drug discovery for this crucial target, the present study focuses on the development of a new absorbance-based bioassay to search for new semaphorin 3B inducers from natural sources. Among the parameters considered include the type of cancer cell line, the time of incubation, the type of lysis buffer, secondary effects that affect absorbance levels, and ways to minimize false positives. Vitamin D and actinomycin are being used as controls in this assay. Vitamin D acts as a positive control since it is a semaphorin 3B inducer. Comparison of the levels of induction of the active substances to that of the positive control provides an indication about the level of potential a hit will have if being developed as a drug. Actinomycin inhibits transcription by binding to DNA at the transcription initiation level. When using actinomycin in this assay, its effect is considered to be proportional to that of semaphorin 3B inhibitors. Hence, actinomycin serves as a negative control to discriminate inducers from inhibitors of semaphorin 3B. The use of both controls, therefore, offers the opportunity to discover selective and highly potent semaphorin 3B inducers of natural origin. The assay has been standardized in a 96-well plate format to optimize sensitivity, selectivity, accuracy, robustness, and cost effectiveness. A library of natural product compounds isolated from higher plants, filamentous fungi, and cyanobacteria is currently being screened using this new bioassay. A total of 50 samples have been tested already with two samples exhibiting low induction levels. The most active substances will be further tested using a series of immunoblot secondary assays to validate the potential hits. Additionally, the screening assay presented could be modified to discover new small molecules or drug-like scaffolds as inhibitors or inducers of other semaphorins. Thus, an assay to identify compounds that selectively and potently affect this pathway may lead to new ways of understanding the cell signaling mechanism of these agents, which could be beneficial for the discovery of new natural product leads for cancer treatment. Program project grant P01-CA125066-S1 funded by the National Cancer Institute, NIH. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2837. doi:1538-7445.AM2012-2837
COMMIT Anti-Smoking Program Shows Modest Success
Authors: S. Jenks, L. Anderson
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article COMMIT Anti-Smoking Program Shows Modest Success Get access Susan Jenks, Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Anderson Linda Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 5, 1 March 1995, Pages 343–344, https://doi.org/10.1093/jnci/87.5.343 Published: 01 March 1995
Case 23-2013
Authors: Kamyar Kalantar-Zadeh, Raul N. Uppot, Kent B. Lewandrowski
Journal: New England Journal of Medicine (2013)

A 54-year-old woman with type 2 diabetes mellitus was admitted to the hospital because of abdominal pain, vomiting, and confusion. Initial laboratory evaluation revealed a serum lactate level of 20.3 mmol per liter and a venous blood pH of 6.62. A diagnosis was made.
OT1-02-09: A Phase II Randomized Trial of Lapatinib with Either Vinorelbine or Capecitabine as First- and Second-Line Therapy for HER2−Overexpressing Metastatic Breast Cancer.
Authors: W Janni, J Pikiel, T Sarosiek, B Karaszewska, CA Papadimitriou, K Schwedler, Gallego J Alavarez, M Caruso, RA Herve, MR Lau, LS Williams, K Briggs, FJ Sapunar
Journal: Cancer Research (2011)

Abstract Background: Lapatinib, a dual kinase inhibitor of epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER2/ErbB2), is approved for the treatment of HER2−overexpressing (HER2+) metastatic breast cancer (MBC) in combination with capecitabine following progression after trastuzumab, anthracyclines, and taxanes. Vinorelbine is an important chemotherapy option in MBC, and multiple phase II trials in combination with trastuzumab have been conducted. Methods: This randomized, open-label, multicenter, phase II study (VITAL, LAP112620, NCT01013740) is evaluating the efficacy and safety of lapatinib with either vinorelbine or capecitabine in women with HER2+ MBC. A total of 105 stage IV breast cancer patients with disease progression who have received ≤1 chemotherapy regimen in the metastatic setting with an ECOG performance status of ≤1 are randomized 2:1 to either: lapatinib 1250 mg orally once daily (QD) continuously plus vinorelbine 20 mg/m2 intravenously on days 1 and 8 every third week; or lapatinib 1250 mg orally QD continuously plus capecitabine 2000 mg/m2/d orally in 2 doses 12 hours apart on days 1 to 14 every third week. Following progression in the randomized phase, patients will be given the option to cross over to the other arm. The primary endpoint is progression-free survival and will be analyzed with a descriptive intent since the study is not powered to detect differences between treatment arms. Secondary endpoints include overall response rate, overall survival, duration of response, time to response, and clinical benefit rate. The study is currently recruiting in 8 countries in Europe (Bulgaria, France, Germany, Greece, Italy, Poland, Serbia, Spain) and 2 in Latin America (Chile, Mexico). Funding Source: GlaxoSmithKline Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-09.
Abstract 2212: C-terminus-truncated hepatitis B virus X protein enhances cell invasiveness in hepatocellular carcinoma
Authors: Karen Man-Fong Sze, Glanice Kin-Yan Chu, Irene Oi-Lin Ng
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma (HCC) is the fifth of major malignancies worldwide and chronic hepatitis B virus (HBV) infection is one of its well known risk factors. Random integration of the HBV DNA into host genome is frequent in human HCCs and this leads to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). In this study, we investigated the frequency of this C-terminal truncation of HBx in human HCCs and its functional significance in HCC cells. In the 51 HBV-positive patients with HCC, full-length HBx was detected in all of the non-tumorous livers. Interestingly, natural COOH-truncated HBx was found in 47% tumours. Upon clinicopathological analysis, presence of natural COOH-truncated HBx significantly correlated with the presence of venous invasion, a hallmark of metastasis (p &amp;lt; 0.01). Doxycycline- inducible stable expression of the full-length HBx and C-terminal truncated forms of HBx in HepG2 cells was employed for in vitro cell invasion assay and cell signalling analysis involved in cell invasiveness. Inducible expression of COOH-truncated HBx protein (with 24 amino acids truncated at C-terminal end) in HepG2 cells enhanced cell invasiveness, and C-Jun transcriptional activity, and increased MMP10 transcription production, as compared with the full-length HBx. The activation of the MMP10 promoter by the COOH-truncated HBx was abolished when the AP-1 binding sites were mutated. Our data suggest that COOH-truncation of HBx may play a significant role in enhancing cell invasiveness and metastasis in HCC, possibly via activation of the MMP10 through C-Jun signaling pathway. (This study was supported by a Hong Kong Government RFCID grant 05050022) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2212. doi:1538-7445.AM2012-2212
1085 ABROGATION OF TUMOR-ASSOCIATED IMMUNOSUPPRESSION BY TARGETING TUMOR-INFILTRATING REGULATORY T-CELLS RESTORES IMPAIRED T CELL RESPONSES IN PATIENTS WITH LIVER CANCER
Authors: A. Pedroza-Gonzalez, J. Kwekkeboom, E.T. Tjwa, W.G. Polak, D.J. Grünhagen, J.N.M. Ijzermans, H.L.A. Janssen, D. Sprengers
Journal: Journal of Hepatology (2013)
Determination of Extent and Activity With Radionuclide Imaging in Erdheim-Chester Disease
Authors: C Franzius, J Sciuk, C Bremer, M Kempkes, O Schober
Journal: Clinical Nuclear Medicine (1999)

Erdheim-Chester disease usually involves the diaphyseal and metaphyseal regions of tubular bones and various visceral organs. A 56-year-old woman presented with the histologically confirmed diagnosis of Erdheim-Chester disease. A Tc-99m MDP bone scan revealed the entire extent of the skeletal disease and showed unusual involvement of the epiphyses and axial skeleton. In addition to MRI, a Ga-67 citrate scan including SPECT showed extensive soft-tissue infiltration of different organs. Both Tc-99m MDP and Ga-67 scintigraphy are useful tools in determining the distribution of this rare disease.