tbuckley/cabot-search huggingface dataset:
Abstract 5735: Synthesis and characterization of PEG-ylated porphyrins for targeting the epidermal growth factor receptor in colorectal cancer detection
Authors: Russell J. Ledet, Krystal Fontenot, Graça H. Vicente
Journal: Cancer Research (2012)

Abstract ABSTRACT According to the National Cancer Institute, an estimated 102,900 (colon) and 39,670 (rectal) new cases were obtained in 2010. An estimated 51,370 people have died from colon and rectal cancers combined. This makes colorectal cancer (CRC) the second leading cause of cancer-related deaths in the United States. Consequently, the development of an in-vivo imaging agent that is selective for CRC has long been needed. Much of the detection for tumorigenesis relies on the efficacy in detecting small tumors. Current agents are not selective and often stain tissue not associated with the cancer cells making it difficult to delineate between viable and tumorigenic entities. This project introduces a novel macrocycle conjugated to polyethylene glycol linker, which we hypothesize will serve as the template for a selective molecule with high fluorescence yields that greatly increases earlier detection. Our targeted remedy is a porphyrin that is conjugated to a peptide with an affinity for the Epidermal Growth Factor Receptor (EGFR). Porphyrins are characteristically aromatically stable, contain trademark absorption bands in the visible and near-IR range, and have fluorescence quantum yields much above the current fluorophores. This makes the macrocycle optimal for confocal laser endomicroscopy (CLE) agent production. Consequently, we use a polyethylene glycol linker in order to increase water solubility, retain low toxicity, and to achieve high fluorescence quantum yields, as well as high conjugation yields. In this research, we were able to produce both precursors to the porphyrin-peptide conjugate, MesoPOR-(mono)-3PEG and MesoPOR-(di)-3PEG. These molecules were synthesized successfully with the use of peptide conjugation mechanisms. Molecular weights were confirmed using Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS). Characterization was performed using 1H Nuclear Magnetic Resonance (1H-NMR) and Ultraviolet-Visible Spectroscopy (UV-Vis) of the intended molecules. The synthesized molecules, MesoPOR-(mono) 3PEG and MesoPOR-(di) 3PEG, will be useful in peptide conjugation that targets EGFR. These peptide ligands will increase selectivity and detect CRC via CLE. 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 5735. doi:1538-7445.AM2012-5735
Abstract 5371: Epigenetic regulation in skin cancer: global DNA methylation profiling in DMBA/TPA induced mice.
Authors: Jong Hun Lee, Limin Shu, Mou-Tuan Huang, Allan H. Conney, Ah-Ng Tony Kong
Journal: Cancer Research (2013)

Abstract Hypermethylation of CpG islands in the promoter regions of tumor suppressor genes is postulated to be the most relevant epigenetic changes resulting in gene silencing of tumor suppressor gene in cancer. Transcriptionally repressed genes by epigenetic regulation can be reactivated by epigenetic modifications because these silenced genes are still genetically intact. Thus, it is relevant to profile global DNA methylation changes that occur in early stages of carcinogenesis (Jones &amp; Baylin, 2002). To begin addressing this issue, we conducted global profiling of DNA methylation changes in a well-established multistage skin carcinogenesis model using methylated DNA immunoprecipitation (Medip) coupled with CpG island microarray. Tumorigenesis was induced by sequential topical application of mutagen 7,12-Dimethylbenz(a)anthracene (DMBA), and promoting agent 12-O-tetra-decanoylphorbol-13-acetate (TPA), on the dorsal skin of normal CD-1 mice. After 12 weeks, animals were sacrificed and DNA extracted from papillomas. Methylation enriched DNA fragments were pulled down and hybridized to CpG microarray covering 16,030 CpG islands (Agilent, Santa Clara, CA) The results show that significant changes in DNA methylation profile between normal skin and DMBA/TPA induced papilloma, analyzed by Genespring and Bioconductor. After normalization of probe with the gene, 186 genes from 9,867 of up-regulated methylation genes showed at least average 2-fold changes and these include some DNA damage and repair, oxidative stress and inflammatory genes such as Gadd45b and Arnt2. In summary, DMBA/TPA induced mouse skin papilloma undergo extensive aberrant CpG island hypermethylation. Genes detected from Medip-chip assay may be utilized as a potential epigenetic tool to study skin cancer. Jones, P. A., &amp; Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nature Reviews Genetics, 3, 415-428. Citation Format: Jong Hun Lee, Limin Shu, Mou-Tuan Huang, Allan H. Conney, Ah-Ng Tony Kong. Epigenetic regulation in skin cancer: global DNA methylation profiling in DMBA/TPA induced mice. [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 5371. doi:10.1158/1538-7445.AM2013-5371
Abstract 4310: TWIST1, a B-RAF effector, promotes invasion and is a novel regulator of MMP-1 in human melanoma cells
Authors: Michele B. Weiss, Ethan V. Abel, Melanie M. Mayberry, Andrew E. Aplin
Journal: Cancer Research (2012)

Abstract Metastatic melanoma is the deadliest form of skin cancer due to its highly aggressive and chemotherapy-resistant nature. Therefore, determining the factors impacting melanoma advancement toward metastasis is an important and clinically-relevant task. Importantly, RAF/MEK/ERK signaling is hyperactive in the great majority of melanoma cells and is a driver of melanoma growth and invasion. In addition, the TWIST1 protein is up-regulated in melanoma and its expression correlates strongly with poor clinical prognosis. However, the mechanism underlying TWIST1 up-regulation, as well as the role of high TWIST1 expression in traits associated with the progression of melanoma, has yet to be uncovered. In this study, we report that disruption of RAF/MEK/ERK signaling strongly represses TWIST1 at the mRNA and protein level. We further show that TWIST1 protein levels are especially high in B-RAF mutant cells as well as in vertical growth phase melanoma cells, which are those that first begin to invade downward into the deeper dermal layers eventually leading to metastasis. To that effect, depletion of TWIST1 in several invasive melanoma cell lines significantly reduces Matrigel invasion. The inverse phenotype is apparent when TWIST1 is overexpressed in low TWIST1-expressing, non-invasive melanoma cell lines. Additionally, we tested the effect of altered Twist expression in three-dimensional collagen spheroid outgrowth assays, which mimic both tumor architecture and the in vivo collagen-rich dermal layer. We observe significant reduction in spheroid outgrowth when invasive cell lines are depleted for TWIST1 as well as increases in outgrowth when non-invasive cells overexpress TWIST1. Alterations to spheroid outgrowth were not as a result of apoptotic changes or proliferative rate. Importantly, we have found matrix metalloproteinase-1 (MMP-1) to be a downstream effector of TWIST1. Furthermore, TWIST1 acts as a mediator between activated B-RAF signaling and MMP-1 in a dose-dependent and direct manner at the level of transcription. Our findings uncover the novel interplay between B-RAF, TWIST1, and MMP-1 which is likely important in the progression of melanoma towards metastasis. 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 4310. doi:1538-7445.AM2012-4310
Summary of Institute of Medicine Study of Resources for Clinical Investigation
Authors: K. H. Antman
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Summary of Institute of Medicine Study of Resources for Clinical Investigation Get access Karen H. Antman Karen H. Antman * Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical SchoolBoston, MA. *Correspondence to: Dr. Karen H. Antman, Department of Medicine, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 6, 15 March 1989, Pages 402–403, https://doi.org/10.1093/jnci/81.6.402 Published: 15 March 1989 Article history Received: 14 February 1989 Accepted: 15 February 1989 Published: 15 March 1989
THU0061 Anemia in patients with rheumatoid arthritis: A cross-sectional study
Authors: J. Back, E. Baecklund, G. Birgegard
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anemia has been a common clinical problem in rheumatoid arthritis (RA), in earlier studies reported in 30-60% of RA patients (1). There are few studies of the frequency and type of anemia in RA since the introduction of biologic drugs and more active anti-rheumatic therapy. <h3>Objectives</h3> Study the frequency and type of anemia in patients with RA and correlate the findings to clinical characteristics and therapy. <h3>Methods</h3> Cross-sectional study. All patients with follow-up for RA at the department of rheumatology, Uppsala University Hospital, Sweden were identified and information about lab variables and clinical data were collected from the medical records. RA was defined according to the 1987 ACR criteria and anemia according to the WHO definition (hemoglobin&lt;120 g/L for women and &lt;130 g/L for men). <h3>Results</h3> A total of 1106 patients with RA were identified (mean age 62.6 years, 74.1% women, 75.4% RF-positive). Of the 1106 patients 173 (15.6%) had anemia (17.8% of the men and 14.9% of the women). The anemia was microcytic (mean cell volume &lt;82) in 15.6% of the women and 3.9% of the men. Increased CRP was more common among the anemic patients (71% had CRP&gt;5 mg/L) than in RA patients without anemia (37% with CRP&gt;5mg/L). No significant difference of the frequency of anemia was seen with different drug therapy or among the different biologic drugs (based on low numbers of anemic patients on each biologic drug). Anemia was present in 11.8% of patients treated with biologic drugs, 13.6% of methotrexate-treated patients and in 14.2% of patients treated with NSAIDs on regular basis. <h3>Conclusions</h3> The occurrence of anemia in contemporary RA patients seems lower than in earlier studies, but still, in this setting, a substantial part of all RA patients and of patients on biologic therapy (15.6% and 11.8%, respectively) had anemia. Inflammatory activity, as mirrored by elevated CRP, is correlated to the presence of anemia. Increasing knowledge of the mechanisms behind RA-associated anemia now opens for new therapeutic possibilities (2). The benefit and role of specific anemia therapy for these patients remains to be determined. <h3>References</h3> Wilson A. Prevalence and outcomes of anemia in rheumatoid arthritis: A systemic review of the literature. Am J Med 2004; 116 (7A): 50S-57S. Andrews NC.Forging a field: the golden age of iron biology.Blood. 2008 Jul 15;112(2):219-30. <h3>Disclosure of Interest</h3> None Declared
Abstract 3036: Interaction of proliferation cell nuclear antigen (PCNA) with c-Abl in cell proliferation and response to DNA damages in breast cancer
Authors: Hua Jun Zhao, Po-Chun Ho, Yuan-Hung Lo, Alexsandra Espejo, Mark T. Bedford, Mien-Chie Hung, Shao-Chun Wang
Journal: Cancer Research (2012)

Abstract Cell proliferation in primary and metastatic tumors is a fundamental characteristic of advanced breast cancer. Further understanding of the mechanism underlying enhanced cell growth will be important in identifying novel prognostic markers and therapeutic targets. Here we demonstrated that tyrosine phosphorylation of the proliferating cell nuclear antigen (PCNA) is a critical event in growth regulation of breast cancer cells. We found that phosphorylation of PCNA at tyrosine 211 (Y211) enhanced its association with the non-receptor tyrosine kinase c-Abl. We further demonstrated that c-Abl facilitates chromatin association of PCNA and is required for nuclear foci formation of PCNA in cells stressed by DNA damage as well as in unperturbed cells. Targeting Y211 phosphorylation of PCNA with a cell-permeable peptide inhibited the phosphorylation and reduced the PCNA-Abl interaction. These results show that PCNA signal transduction has an important impact on the growth regulation of breast cancer cells. 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 3036. doi:1538-7445.AM2012-3036
Abstract 2895: Phylogenetic models of tumor progression from fluorescence in situ hybridization (FISH) data on many single cells of a solid tumor.
Authors: Salim A. Chowdhury, Alejandro A. Schäffer, Stanley E. Shackney, Darawalee Wangsa, Kerstin Heselmeyer-Haddad, Thomas Ried, Russell Schwartz
Journal: Cancer Research (2013)

Abstract Purpose: Characterizing the common pathways through which tumors progress is critical to understanding the molecular basis of cancer and developing effective treatments. Algorithms for phylogenetics, i.e., evolutionary tree building, can be used to infer progression pathways of single tumors when there is widespread intra-tumor heterogeneity from cell to cell. We describe computational methods to compute likely evolutionary histories from single-cell copy number data and apply the methods to single-cell gene copy number data derived from paired primary and metastatic samples of cervical cancers. Materials and methods: The inputs to our methods are lists of cell types for each patient sample, where a cell type is an array of copy numbers of gene probes measured by FISH. In the cervical cancer data set, copy numbers of four genes (LAMP3, PROX1, PRKAA1 and CCND1) were measured on up to 250 cells each of paired primary and metastatic samples from 16 patients. An example of a cell type is (4, 1, 3, 2). Our algorithms derive maximum parsimony phylogenetic trees explaining how all observed cell types might have evolved from a common diploid ancestor (2,2,2,2), seeking to explain the observed cells with as few copy number changes as possible across the tree. Due to the computational difficulty, we apply a heuristic algorithm to infer an approximately optimal tree by identifying likely unobserved ancestral cell states through a variant of the median joining method and then find the most parsimonious tree connecting these states. Our software also includes a method of computing consensus trees that facilitate the comparison of the tree models for each primary/metastasis sample pair. Results and Conclusion: Our methods allow us to build models of evolution of single tumors at the cellular level that provide insights into possible progression pathways and varying selective pressures in primary and metastatic sites. Analysis of tree geometry shows significant variability in evolutionary patterns between primary and metastatic sites consistent with more specific selective pressures in the metastases. Analysis of specific patterns of gene gain or loss in each environment shows a complicated portrait of tumor evolution with substantial variability from patient to patient. Citation Format: Salim A. Chowdhury, Alejandro A. Schäffer, Stanley E. Shackney, Darawalee Wangsa, Kerstin Heselmeyer-Haddad, Thomas Ried, Russell Schwartz. Phylogenetic models of tumor progression from fluorescence in situ hybridization (FISH) data on many single cells of a solid tumor. [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 2895. doi:10.1158/1538-7445.AM2013-2895
Speaking out for the aging population
Authors: J. T. de Alvarez
Journal: BMJ (1997)

The first thing you notice about Julia Alvarez is her enthusiasm, then her fluff of snowy white hair and bright red suit. The next things you notice are her intelligence, persistence, and willingness to speak out.

Last week, for example, she told Kofi Annan, the United Nation's secretary general, to put his own house in order on issues of aging. In June he had called for a “rejuvenation” of the UN workforce-whose average age is 49, which he said was “far too high.” The UN's mandatory retirement age is 60 or 62, depending on when an employee was hired. “Nowhere in the UN charter does it say people have to retire at 60,” she said. “Strangely enough, the political posts-secretary general, undersecretary generals, assistant secretary generals, and heads of agencies-do not have a mandatory retirement age,” she told a non-governmental organisation's committee meeting on aging.

Julia Alvarez, now 71, has led a bicultural, bilingual, binational life. She went to boarding school in New York and graduated in 1948 from the Connecticut College for Women with a degree in psychology and sociology. Soon after, she married Dr Eduardo Alvarez, a surgeon, and had two daughters. They moved back to …
Abstract 2197: A robotic genome-scale shRNA screen identifies metabolic drug targets and a glioblastoma gene signature
Authors: Marco Colombi, Don Benjamin, Michael N. Hall, Anke Thiemeyer, Klaus Molle, Christoph Moroni
Journal: Cancer Research (2010)

Abstract Proteins encoded by oncogenes represent suitable drug targets and several have been validated clinically. However, certain non-oncogenes, which are downstream effectors of oncogenes, may be similarly useful as potential targets of therapy. We have developed a high-throughput strategy using a shRNA genomic library and tumor cells addicted to the mTOR pathway to identify genes (oncogenes or non-oncogenes) which control the oncogenic phenotype. mTOR addicted cells were generated from IL-3 dependent cells following frame-shift mutagenesis and selection for IL-3 independence. mTOR addicted cells obtained from this selection carried frame-shift mutations in the PTEN gene. mTOR addiction was revealed by sensitivity to rapamycin and confirmed biochemically by examining phosphorylation of the mTOR targets S6K and PKB. Interestingly (and of importance to our shRNA-based screening strategy), addition of IL-3 rescued cells from mTOR addiction, as this growth factor antagonized the apoptotic effect of rapamycin. Using robotics (BioMek-NX) and a genomic retroviral shRNA library we evaluated 14’000 genes for a potential role in maintaining mTOR addicted growth. Our strategy was to screen cells in the presence and absence of IL-3 to identify shRNAs that antagonize growth of cells in the absence of IL-3. We identified around 300 genes required for mTOR addicted growth. This set of genes was enriched in highly significant manner for genes known to be involved in cancer, providing proof of concept for the strategy. Examples of identified genes include ras, raf, PKB and mTOR. Also, genes with no cancer link and genes with unknown function were identified. Use of Ingenuity software allowed to place many of the identified genes into functionally distinct groups or pathways. In addition numerous hits affecting metabolic functions, redox functions, and ROS generating systems were identified including the cytoplasmic NADPH complex and complex I-IV of the respiratory chain. Combining the genes et with an Affymetrix gene overexpression analysis in the same cells and analysing by Oncomine software, we identified a glioblastoma gene signature consisting of 13 genes (p-value 2.4E-5) containing 3 oncogenes and several signaling elements. Downregulation of several of these genes in human cancer lines induced apoptosis. Some of he genes identified represent novel potential drug targets. 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 2197.
Charities plead with government not to delay law on foreign aid commitment
Authors: M. Limb
Journal: BMJ (2012)

Experts working to reduce health inequalities around the world have urged the government not to drop plans for a new law to guarantee the United Kingdom’s level of spending on overseas aid.

Anna-Joy Rickard, director of the Humanitarian Centre, a network of organisations that work to reduce global poverty and inequality, told the BMJ , “We are disappointed the government has delayed their commitment to legislate this in parliament, which would have cemented the UK as a leading force against global poverty.

“We join with other non-governmental organisations calling for the government to stick to the timetable they promised.”

The Conservative party made a pre-election pledge to legislate early in government to commit 0.7% of the UK’s national income …
Ethnic Variation in the Incidence, Diagnosis, Prognosis, and Follow-up of Children With Wilms' Tumor
Authors: N. Breslow, A. Olshan, J. B. Beckwith, J. Moksness, P. Feigl, D. Green
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Ethnic Variation in the Incidence, Diagnosis, Prognosis, and Follow-up of Children With Wilms' Tumor Get access Norman Breslow, Norman Breslow Department of Biostatis-tics. University of WashingtonSeattle Correspondence to : Norman Breslow, Ph.D., Department of Biostatistics SC-32, University of Washington, 1959 NE Pacific, Seattle WA 98195. Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrew Olshan, Andrew Olshan Department of Epidemiology, University of North CarolinaChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Bruce Beckwith, J. Bruce Beckwith Department of Pathology, Loma Linda UniversityLoma Linda, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Jami Moksness, Jami Moksness Department of Biostatis-tics. University of WashingtonSeattle Search for other works by this author on: Oxford Academic PubMed Google Scholar Polly Feigl, Polly Feigl Department of Biostatis-tics. University of WashingtonSeattle Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Green Daniel Green Department of Pediatrics, Roswell Park Memorial InstituteBuffalo. N.Y. * See “Notes” section following “References.” Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 1, 5 January 1994, Pages 49–51, https://doi.org/10.1093/jnci/86.1.49 Published: 05 January 1994 Article history Received: 22 April 1993 Revision received: 17 September 1993 Accepted: 29 September 1993 Published: 05 January 1994
A novel hybrid technique using transanal endoscopic microsurgery and balloon dilation in the treatment of a benign complete colorectal anastomotic stricture
Authors: A. Wolthuis, P. Rutgeerts, F. Penninckx, A. D’Hoore
Journal: Endoscopy (2011)

Benign strictures after an anterior resection with double-stapled anastomosis remain a problem with an incidence rate of 8 % [1]. Usually, a coloanal or colorectal anastomosis can be treated conservatively with digital and bougie (Hegar) dilation or balloon dilation, respectively. If the rectal ampulla is preserved and the colorectal stricture is high, operative resection with creation of a new anastomosis might be indicated if balloon dilation is impossible or fails. Transanal endoscopic microsurgery (TEM)-assisted balloon strictureplasty could be a minimally invasive solution to bridge the gap between radical surgery and conservative treatment.