tbuckley/cabot-search huggingface dataset:
Abstract 227: Estrogen receptor-α and tumor initiating cells are novel targets of diallyl trisulfide in breast cancer cells
Authors: Eun-Ryeong Hahm, Su-Hyeong Kim, Shivendra V. Singh
Journal: Cancer Research (2014)

Abstract Epidemiological studies suggest a protective role for Allium vegetables, such as garlic, against breast and other cancers. Diallyl trisulfide (DATS) is a promising oil-soluble anticancer metabolite generated after cutting or chewing of Allium vegetables. We have shown previously that DATS inhibits viability of human breast cancer cells (MCF-7 and MDA-MB-231) and a cell line derived from spontaneously developed tumor of a mouse mammary tumor virus-neu mouse by causing apoptosis induction. We also found that a non-tumorigenic normal human mammary epithelial cell line (MCF-10A) is resistant to cell death induction by DATS. Studies by others have demonstrated in vivo efficacy of DATS against MCF-7 xenografts in nude mice. The present study builds upon these observations and identifies novel targets of DATS in breast cancer cells. MCF-7 and T47D cells exposed to DATS exhibited downregulation of estrogen receptor-α (ER-α) protein, which peaked between 12 and 24 h post-treatment. Diallyl sulfide and diallyl disulfide analogs were relatively less effective in suppressing protein level of ER-α compared with DATS. The 17β-estradiol (E2)-induced expression of pS2, an ER-α target gene product, was also decreased in the presence of DATS. Downregulation of ER-α protein expression resulting from DATS treatment was accompanied by a decrease in nuclear level of ER-α, suppression of ER-α mRNA, and inhibition of ERE2e1b-luciferase reporter activity. Moreover, apoptotic cell death induced by DATS was partially but statistically significantly attenuated in the presence of E2 in MCF-7 cells as well as by overexpression of ER-α in MDA-MB-231 cells. DATS treatment inhibited breast cancer stem cell (bCSC) population as evidenced by flow cytometric analysis of CD44high/CD24low/epithelial specific antigen positive population, aldehyde dehydrogenase 1 activity, and mammosphere frequency in MCF-7 and SUM159 cells. Inhibition of bCSC by treatment with DATS was associated with downregulation of EZH2 and Kruppel-like factor 4 proteins in both MCF-7 and SUM159 cells. In conclusion, the present study identifies ER-α and bCSC as novel targets of DATS in mammary cancer cells. This study was supported by the grant RO1 CA113363-09 awarded by the National Cancer Institute. Citation Format: Eun-Ryeong Hahm, Su-Hyeong Kim, Shivendra V. Singh. Estrogen receptor-α and tumor initiating cells are novel targets of diallyl trisulfide in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 227. doi:10.1158/1538-7445.AM2014-227
Presence of bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
Authors: José M. González-Navajas, Pablo Bellot, Rubén Francés, Pedro Zapater, Carlos Muñoz, Juan Carlos García-Pagán, Sonia Pascual, Miguel Pérez-Mateo, Jaime Bosch, José Such
Journal: Journal of Hepatology (2007)
Letter: Primary responses to transplantation antigens.
Authors: G D Bonnard, L Lemos, E Gautier
Journal: BMJ (1974)

tinue to use celphaloridine as a local applica- tion in the proiphylaxis of potentially con- taminated wounds.We are indebted to Glaxo Research Ltd. for the supply of cephaloridine (Ceporin) and Aspro-Nicholas Ltd. for the gentamicin (Genticin).-Weare, etc.,
Candida and Candidosis
Authors: John W. Rippon
Journal: JAMA (1989)

This monograph on<i>Candida</i>and its associated diseases is an update of the first edition published in 1979. That volume brought together a comprehensive and in-depth analysis of the clinical disease types as no previous monograph on the subject had done. Dr Odds' very thorough analysis of the infections, both systemic and cutaneous, was accompanied by a long analysis of treatment modalities that had been tried and the results obtained. This was extremely important, say, in trying to evaluate world experience for the therapy for chronic vaginitis or the significance of recurrent thrush. The emerging diseases of the day were also covered. These were the serious opportunistic infections that were now appearing in the immunosuppressed host. His very readable text then gave the reader a comprehensive understanding of the disease processes. Excellent historical perspectives were also included, along with a thorough overview of the basic biology, mycology, serology, and experimental
The kindest insult
Authors: J. Han
Journal: BMJ (2003)

That Mrs Park wore a woollen overcoat and scarf on an unusually warm spring afternoon was not disconcerting to me. After all, this uniform is typical of many mentally ill elderly folk living a tenuous existence on the streets of San Francisco. Her paranoid rants about the end of the world and the neighbours who were spying on her also left me unmoved. What was painfully upsetting to me, however, was the anger and offence she took at my need for a Korean language interpreter.

> Mrs Park stopped growling and gesticulating long enough to appear hurt 

“If he is Korean, why does he need someone to speak his language for him?” Mrs Park exhorted through the translator as she eyed me suspiciously. The interpreter shifted nervously through her own embarrassment as she channelled this message to me.

Having grown up in the only Korean family within several counties in rural Ohio, I did not place learning my “native tongue” high …
Doctors can force woman to have lifesaving treatment
Authors: C. Dyer
Journal: BMJ (2010)

A high court judge in England has ordered that doctors can force a woman without the capacity to decide for herself to have lifesaving treatment for aplastic anaemia.

Mrs Justice Hogg made the ruling in the Court of Protection after an unnamed NHS trust applied to the court with the backing of the Official Solicitor, who looks after the interests of those lacking capacity.

The judge said the 30 year old woman, named only as SB, who is detained under the Mental Health Act, has a serious psychiatric disorder and lacks the capacity to decide for …
Prevalence of Symptomatic Pelvic Floor Disorders in US Women
Authors: Ingrid Nygaard, Matthew D. Barber, Kathryn L. Burgio, Kimberly Kenton, Susan Meikle, Joseph I Schaffer, Cathie Spino, William E. Whitehead, Jennifer Wu, Debra J. Brody
Journal: JAMA (2008)

ELVIC FLOOR DISORDERS INclude urinary incontinence, pelvic organ prolapse, fecal incontinence, and other sensory and emptying abnormalities of the lower urinary and gastrointestinal tracts.A regional study in the United States found that almost 10% of women have surgery for urinary incontinence, pelvic organ prolapse, or both during their lifetime, and 30% of those women have 2 or more surgical procedures. 1 However, because no single national population-based survey has assessed the prevalence of the 3 major pelvic floor disorders in US women, the national burden related to these diseases remains unknown.Thus, in 2003, the Pelvic Floor Disorders Network (PFDN) submitted a proposal to add questions about pelvic floor disorders to the 2005-2006 National Health and Nutrition Examination Survey (NHANES).The PFDN, a clinical trials network of investigators from 7 clinical centers and a data coordinating center, is supported by the
The Future of Pharmaceuticals: The Changing Environment for New Drugs
Authors: Louis Lasagna
Journal: JAMA (1981)

Bezold has compiled a series of briefing papers and discussion summaries from some seminars intended to expose congressional staff people to the forces affecting drug discovery and development. As Alvin Toffler says in the book's foreword, "today's rapid... changes are making our political institutions obsolete.... [The] US Congress today is... deluged with data it can neither digest properly nor apply intelligently." Amen. The book begins with a look at past predictions about medical progress as well as a guess about the future. Estimates made in 1968 and 1976 were dead right in some respects (H<sub>2</sub>blockers, for example) and dead wrong in others (such as the widespread utility of laboratory tests for cancer screening). Concern is expressed about the impact of the Kefauver-Harris Amendments (and the implementing regulations) on the cost and success of drug discovery and on pharmaceutical incentives. Most of the opinions and data do not generate
Colorectal Carcinoma Invasion Inhibition by CO17-1A/GA733 Antigen and Its Murine Homologue
Authors: Saroj Basak, David Speicher, William Wunner, Gerd Maul, Dorothee Herlyn, Stephen Eck, Michael S. Simmons
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The gastrointestinal carcinoma antigen GA733 is a potential target for passive and active immunotherapy for patients with colorectal carcinoma. This antigen has been characterized previously as a homophilic adhesion (i.e., adhesion to self) protein, but the functional consequences of homophilic adhesion for tumor growth and invasion are unknown. The availability of a murine homologue of GA733, i.e., murine epithelial glycoprotein (mEGP), allows for functional analysis of cell adhesion as it relates to tumor growth and invasion, both in vitro and in vivo. Methods: CT-26 murine colorectal carcinoma cells were transfected with complementary DNAs encoding either the human or the murine antigen. GA733- or mEGPproducing cells were evaluated for homophilic adhesion, growth on plastic surfaces, colony formation in soft agar, and invasion through a reconstructed basement membrane (Matrigel). mEGP-producing cells were also examined for their capacity to metastasize in mice. Reported P values are two-sided. Results: Compared with control cells, mEGP-producing cells showed significantly lower growth rates, colony formation, and invasion through Matrigel in vitro (all P values <.05). Compared with vector-only transfected cells and parental cells, mEGP-producing cells showed a reduction in metastatic potential in syngeneic immunodeficient and immunocompetent mice (all P values <.05). In contrast to mEGPtransfected cells, GA733-transfected cells did not exhibit significantly reduced growth or colony formation in vitro (all P values >.05). However, GA733-transfected cells did show reduced invasion through Matrigel compared with vector-only transfected cells or parental cells (all P values <.05). Conclusion: The adhesion proteins GA733 and mEGP inhibit invasion of tumor cells.
Chemosensitizers to Overcome and Prevent Multidrug Resistance?
Authors: U. A. Germann, M. W. Harding
Journal: JNCI Journal of the National Cancer Institute (1995)

testinal crypt cells contain higher levels of cytoskeletal-associated pp60 r protein tyrosine kinase activity than do differentiated enterocytes. Oncogene 1993;8:1033-9. (12) Park J, Meisler AI, Cartwright CA. c-Yes tyrosine kinase activity in human colon carcinoma. Oncogene 1993:8:2627-35. (13) Cross FR, Garber EA, Pellman D, Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and forced transformation. Mol Cell Biol 1984:4:1834-42. (14) Hamaguchi M, Hanafusa H. Association of p60 with Triton S100-resistant cellular structure correlates with morphological transformation. Proc Natl Acad Sci U S A 1987;84:2312-6. (15) Rudnick DA, McWherter CA, Gokel GW, Gordon JI. MyristolCoA:protein /V-Myristoyltransferase. Adv Enzymol Relat Areas Mol Biol 1993:67:375-430. (16) Johnson DR, Bhatnagar RS, Knoll LJ, Gordon JI. Genetic and biochemical studies of protein /V-myristoylation. Annu Rev Biochem 1994,63:869-914. (17) Mcllhinney RA, McGlone K, Willis AC. Purification and partial sequencing of myristoyl-CoA:protein /V-myristoyltransferase from bovine brain. Biochem J 1993;290(Pt 2):405-10. (18) King MJ, Sharma RK: Mechanisms of action of NIP71 on JV-myristoyltransferase activity. Mol Cell Biochem 1994; 141:79-86. (19) Glover CJ, Felsted RL. Identification and characterization of multiple forms of bovine brain /V-myristoyltransferase. J Biol Chem 1995; 270:23226-33. (20) Heuckeroth RO, Glaser L, Gordon JI. Heteroatom-substituted fatty acid analogs as substrates for /V-myristoyltransferase: an approach for studying both the enzymology and function of protein acylation. Proc Natl Acad Sci USA 1988:85:8795-9. (2/) Bryant M, Ratner L. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci U S A 1990;87:5237. (22) Heuckeroth RO, Gordon JI. Altered membrane association of P60v-src and a murine 63-kDa /V-myristoyl protein after incorporation of an oxygen-substituted analog of myristic acid. Proc Natl Acad Sci U S A 1989:86:5262-6. (23) Devadas B, Zupec ME, Freeman SK, Brown DL, Nagarajan S, Sikorski JA, et al. Design and syntheses of potent and selective dipeptide inhibitors of Candida albicans Myristoyl-CoA:protein /V-myristoyltransferase. J Med Chem 1995:38:1837-40. (24) Mcllhinney RA. The fats of life: the importance and function of protein acylation. Trends Biochem Sci 1990:15:387-91.
Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.
Authors: F Falcioni, Z Dembic, S Muller, P V Lehmann, Z A Nagy
Journal: The Journal of Experimental Medicine (1990)

Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.
CARRIERS OF THE KIF6 719ARG ALLELE APPEAR TO HAVE A HIGHER LP(A) CONCENTRATION AND PREDOMINANTLY SMALL LDL PARTICLES DESPITE SIMILAR TRADITIONAL LIPOPROTEIN LEVELS
Authors: Juan J. Rivera, Khurram Nasir, Xi Zhu, Robert Superko, Roger S. Blumenthal, Arthur S. Agatston
Journal: Journal of the American College of Cardiology (2011)
Oxygen consumption and coronary reactivity in postischemic myocardium.
Authors: D D Laxson, D C Homans, X Z Dai, E Sublett, R J Bache
Journal: Circulation Research (1989)

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/- 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.
Ethics of Abortion, Sterilization, and Birth Control
Authors: L. Riddell
Journal: BMJ (1932)

At the opening of the second winter session of the Hampstead General and North-West London Hospital Post-Graduate School, on January 6th, an address was delivered by Lord RIDDELL, who took as his subject "The ethics of abortion, sterilization, and birth control."Lord Riddell said that the much-discussed subject of abortion raised questions of supreme difficulty.The practice was one which few of the ancients before the Christian era seriously condemned.Certain Greek philosophers, notably Plato and Aristotle, expressed them- selves directly in its favour.Abortion was not expressly prohibited by the Mosaic law, and the New Testament was silent on the subject.The Christian Fathers declared that " one identical life principle exists from conception to death," and that consequently abortion at any stage was murder.That was still the Roman Catholic view.The Jews, on the contrary, regarded abortion as justifiable when performed to protect the mother.
Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition
Authors: Giada Gelsomino, Paola A Corsetto, Ivana Campia, Gigliola Montorfano, Joanna Kopecka, Barbara Castella, Elena Gazzano, Dario Ghigo, Angela M Rizzo, Chiara Riganti
Journal: Molecular Cancer (2013)

The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors.We studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells.MDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re-activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells.Our work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells.
A Test for Concordance Between the Multilocus Genealogies of Genes and Microsatellites in the Pathogenic Fungus Coccidioides immitis
Authors: M. C. Fisher, G. Koenig, T. J. White, J. W. Taylor
Journal: Molecular Biology and Evolution (2000)

Uncovering the correct phylogeny of closely related species requires analysis of multiple gene genealogies or, alternatively, genealogies inferred from the multiple alleles found at highly polymorphic loci, such as microsatellites. However, a concern in using microsatellites is that constraints on allele sizes may occur, resulting in homoplasious distributions of alleles, leading to incorrect phylogenies. Seven microsatellites from the pathogenic fungus Coccidioides immitis were sequenced for 20 clinical isolates chosen to represent the known genetic diversity of the pathogen. An organismal phylogeny for C. immitis was inferred from microsatellite-flanking sequence polymorphisms and other restriction fragment length polymorphism–containing loci. Two microsatellite genetic distances were then used to determine phylogenies for C. immitis, and the trees found by these three methods were compared. Congruence between the organismal and microsatellite phylogenies occurred when microsatellite distances were based on simple allele frequency data. However, complex mutation events at some loci made distances based on stepwise mutation models unreliable. Estimates of times of divergence for the two species of C. immitis based on microsatellites were significantly lower than those calculated from flanking sequence, most likely due to constraints on microsatellite allele sizes. Flanking-sequence insertions/deletions significantly decreased the accuracy of genealogical information inferred from microsatellite loci and caused interspecific length homoplasies at one of the seven loci. Our analysis shows that microsatellites are useful phylogenetic markers, although care should be taken to choose loci with appropriate flanking sequences when they are intended for use in evolutionary studies.