tbuckley/cabot-search huggingface dataset:
Abstract 5026: B7-H1 confers tumor chemoresistance by regulating MAPK/ERK activation
Authors: Amanda Orzechowski, Haidong Dong
Journal: Cancer Research (2014)

Abstract Development of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of cancer patients. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance has received little consideration. Elevated expression of B7-H1 (also named PD-L1) is predictive of an aggressive disease course, including increases in disease progression and cancer-related mortality in a variety of cancers (ovary, breast, liver, pancreas, esophagus, colon and lung). Although the aggressiveness of B7-H1 positive tumors has been attributed to B7-H1's immune-suppressive function, B7-H1 itself may be directly altering tumor cell intracellular signaling pathways promoting acquisition of drug resistance. It has been reported that overexpression of B7-H1 confers chemoresistance in human cancers. However, the mechanisms by which B7-H1 contributes to tumor chemoresistance have yet to be defined. We show that B7-H1 transfected tumor cells are resistant to chemotherapy. This resistance is due to increased activation of MAPK/ERK pathway in tumor cells with B7-H1 overexpression. Inhibition of ERK activation restored drug sensitivity of B7-H1 positive tumor cells. We further analyzed the downstream elements of B7-H1 signaling pathway and identified a new B7-H1 associated protein that is involved in DNA damage repair and MAPK/ERK activation mechanisms. We conclude that B7-H1 mediates tumor chemoresistance by enhancing the activation of MAPK/ERK pathway via its intracellular signaling pathway. Our studies may identify a novel pharmaceutical target for treatment of B7-H1 positive refractory tumor cells. Citation Format: Amanda Orzechowski, Haidong Dong. B7-H1 confers tumor chemoresistance by regulating MAPK/ERK activation. [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 5026. doi:10.1158/1538-7445.AM2014-5026
HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.
Authors: S D Khare, J Hansen, H S Luthra, C S David
Journal: Journal of Clinical Investigation (1996)

MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs. These mice developed spontaneous arthritis and nail changes in the rear paws. Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area. Transgenic mice expressing HLA-B27 with mouse beta2m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease. Our data demonstrate specific involvement of HLA-B27 'free' HCs in the disease process.
Nitroglycerin causes vasodilatation within ischaemic myocardium
Authors: M W GORMAN, H V SPARKS
Journal: Cardiovascular Research (1980)

Vasodilators such as nitroglycerin have been reported to increase collateral blood flow to ischaemic myocardium. One proposed mechanism of action is dilatation of collateral vessels. The purpose of this study was to determine whether dilatation of vessels within the ischaemic area also contributes to the increase in flow. The left anterior descending coronary artery (LAD) was ligated in chloralose-anaesthetised dogs. Peripheral LAD pressure (PLAD) was measured distal to the occlusion. Myocardial blood flows were measured with 15 μm radioactive microspheres. Ischaemic bed vascular resistance was calculated as PLAD/LAD flow. After 1 h of ischaemia, nitroglycerin (2.3 μg·kg−1·min−1) decreased ischaemic bed resistance by 10% when infused into the LAD, by 16% when infused into the circumflex coronary artery, and by 15% when infused via the right atrium. However, adenosine infusion (2 μg·kg−1·min−1) into the LAD did not decrease ischaemic bed resistance. We conclude that nitroglycerin increases collateral flow in part by dilating large coronary arteries within an acutely ischaemic area
The Rate of Synthesis of Glycosaminoglycans and Collagen by Fibroblasts Cultured from Adult Human Liver Biopsies
Authors: John T. Galambos, Martin A. Hollingsworth, Arthur Falek, W. Dean Warren, J. R. McCain
Journal: Journal of Clinical Investigation (1977)

Adult human liver biopsies were cultured from normal, alcoholic hepatitis, chronic active hepatitis, fibrosis plus alcoholic hepatitis (active cirrhosis), inactive cirrhosis, and drug hepatitis. The synthesis of collagen was estimated in cultures from 58 livers by measuring the conversion of [14C]proline to the [14C]hydroxyproline of collagen; that of glycosaminoglycans in cultures from 57 livers by the incorporation of [3H]acetate and 35SO4 into glycosaminoglycans (GAG). The synthesis of procollagen was increased only in cultures from alcoholic hepatitis, both in the pulse medium (P < 0.05) and in the chase medium (P < 0.02). The synthesis of insoluble collagen was increased in cultures from chronic (active) hepatitis (P < 0.01), fibrosis plus alcoholic hepatitis (active cirrhosis) (P < 0.001), and inactive cirrhosis (P < 0.05). Essentially all radioactive GAG was soluble in culture media. The predominant GAG were chondroitin-4 or -6-SO4. The synthesis of GAG was increased only in cultures from fibrosis plus alcoholic hepatitis (active cirrhosis) both in the pulse medium (P < 0.01) and chase medium (P < 0.001).
Evaluation of percutaneous permeation of repellent DEET and sunscreen oxybenzone from emulsion-based formulations in artificial membrane and human skin
Authors: Tao Wang, Donald Miller, Frank Burczynski, Xiaochen Gu
Journal: Acta Pharmaceutica Sinica B (2014)

Insect repellent DEET and sunscreen ingredient oxybenzone play an essential role in minimizing vector-borne diseases and skin cancers. The purpose of this study was to investigate the effects of emulsion type, addition of thickening agent and droplet size in three emulsion-based lotions on percutaneous permeation of DEET and oxybenzone using in vitro diffusion experiments, in order to minimize overall systemic permeation of the substances. Formulation C (water-in-oil emulsion) significantly increased overall permeation of DEET through human skin (56%) compared to Formulation A (oil-in-water emulsion). Formulation B (oil-in-water emulsion with thickening agent xanthan gum) significantly decreased the size of oil droplet containing DEET (16%), but no effect on oil droplets containing oxybenzone. Adding xanthan gum also increased overall permeation of DEET and oxybenzone (21% and 150%) when compared to Formulation A; presence of both ingredients in Formulation B further increased their permeation (36% and 23%) in comparison to its single counterparts. Overall permeation of oxybenzone through LDPE was significantly higher by 26%-628% than that through human skin; overall permeation of DEET through human skin was significantly higher by 64%-338% than that through LDPE.
Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III
Authors: Sunia Foliaki, Neil Pearce, Bengt Björkstén, Javier Mallol, Stephen Montefort, Erika von Mutius
Journal: Journal of Allergy and Clinical Immunology (2009)
Molecular genetics in clinical practice: evolution of a DNA diagnostic service.
Authors: A. L. Meredith, M. Upadhyaya, P. S. Harper
Journal: BMJ (1988)

The development of a molecular genetics diagnostic service over a three year period was studied in a National Health Service region with a population of three million. Starting from a time when few diagnostic applications were possible, the number of disorders and the overall demand had grown rapidly. Conditions for which molecular genetic diagnosis had been provided included Duchenne and Becker muscular dystrophy, myotonic dystrophy, Huntington9s disease, and cystic fibrosis. Of 405 requests for diagnosis, 151 (37%) related to determination of carrier state, 187 (46%) to determining the feasibility of future prenatal diagnosis, and 67 (17%) were prenatal diagnostic biopsy samples, almost exclusively of first trimester chorion. DNA samples for future diagnostic use with a wide range of genetic disorders had also been banked. The study showed a need for close integration with clinical genetics services to allow satisfactory genetic counselling and interpretation of risks.
Allergenic properties of kiwi‐fruit extract: cross‐reactivity between kiwi‐fruit and birch‐pollen allergens
Authors: V. Voitenko, L. K. Poulsen, L. Nielsen, A. Norgaard, C. Bindslev‐Jensen, P. Stahl Skov
Journal: Allergy (1997)

Our investigation aimed to produce and characterize a kiwi extract and to use this extract to investigate a possible cross‐reactivity with birch pollen. Kiwi was extracted in two buffers: phosphate‐buffered saline (PBS) and borate‐buffered saline (BBS). Extraction in BBS produced a double amount of protein, and a more stabile extract. Tandem crossed‐immunoelectrophoresis showed that the BBS and PBS extracts had several common, but also a few individual, proteins. The mixture of both extracts was assumed to represent the most complete allergen extract. The allergenic properties of the kiwi extract were investigated by immunoblotting (IB), RAST, and histamine‐release (HR) test in 15 birch‐pollen‐allergic patients (eight of them with clinical kiwi allergy) and one with clinical monoallergy to kiwi. All eight birch‐pollen‐allergic patients with kiwi allergy and the kiwi‐monoallergic patient were positive in kiwi IB binding most frequently to proteins of 10‐12 and 20‐25 kDa. With our extract, RAST was positive in four kiwi‐allergic and one non‐kiwi‐allergic patient, whereas the HR test was positive in five kiwi‐allergic patients and negative in all non‐kiwi‐allergic patients. RAST and IB inhibition demonstrated cross‐reactivity between birch‐pollen and kiwi allergens due to a 10‐12 kDa protein. In conclusion, a kiwi extract with allergenic properties was produced, and, by the methods used, cross‐reactivity was demonstrated between birch‐pollen and kiwi allergens.
510 INSULIN RECEPTOR SUBSTRATE-4 INHIBITS AKT/PKB ACTIVITY FORMING A TERNARY COMPLEX WITH SHIP AND EGFR. EFFECT ON HEPG2 CANCER CELL MOTILITY
Authors: E.P. Cuevas, I.D. Román, M.D. Fernández-Moreno, V. Sánchez-Alonso, B. Hernández-Breijo, L.G. Guijarro
Journal: Journal of Hepatology (2009)
Abstract LB-344: Vascular normalization as an emerging strategy to enhance cancer immunotherapy.
Authors: Yuhui Huang, Jianping Yuan, Elda Righi, Dan G. Duda, Dai Fukumura, Mark C. Poznanasky, Rakesh K. Jain
Journal: Cancer Research (2013)

Abstract The recent approval of a prostate cancer vaccine has renewed hope for anti-cancer immunotherapies. However, the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies. Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy, but they are often used at high doses in the clinic to prune tumor vessels and may paradoxically compromise various therapies. Here, we demonstrate that targeting tumor vasculature with lower “vascular normalizing” doses, but not high “anti-vascular/anti-angiogenic” doses of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody results in a more homogeneous distribution of functional tumor vessels. Furthermore, lower doses are superior to the high doses at polarizing tumor-associated macrophages from immune inhibitory M2-like towards immune stimulatory M1-like phenotype, and in facilitating CD4+ and CD8+ T cell tumor infiltration. Based on this mechanism, scheduling lower dose anti-VEGFR2 therapy with T cell activation induced by a whole cancer cell vaccine therapy enhanced anti-cancer efficacy in a CD8+ T cell-dependent manner in both immune tolerant and immunogenic murine breast cancer models. These findings indicate that vascular normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies. Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients, our study suggests a new strategy to more effectively use antiangiogenic agents in breast cancer with active immunotherapy and potentially other anti-cancer therapies. Citation Format: Yuhui Huang, Jianping Yuan, Elda Righi, Dan G. Duda, Dai Fukumura, Mark C. Poznanasky, Rakesh K. Jain. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. [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 LB-344. doi:10.1158/1538-7445.AM2013-LB-344 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
An atlas of over 90,000 conserved noncoding sequences provides insight into crucifer regulatory regions
Authors: Annabelle Haudry, Adrian E Platts, Emilio Vello, Douglas R Hoen, Mickael Leclercq, Robert J Williamson, Ewa Forczek, Zoé Joly-Lopez, Joshua G Steffen, Khaled M Hazzouri, Ken Dewar, John R Stinchcombe, Daniel J Schoen, Xiaowu Wang, Jeremy Schmutz, Christopher D Town, Patrick P Edger, J Chris Pires, Karen S Schumaker, David E Jarvis, Terezie Mandáková, Martin A Lysak, Erik van den Bergh, M Eric Schranz, Paul M Harrison, Alan M Moses, Thomas E Bureau, Stephen I Wright, Mathieu Blanchette
Journal: Nature Genetics (2013)

Despite the central importance of noncoding DNA to gene regulation and evolution, understanding of the extent of selection on plant noncoding DNA remains limited compared to that of other organisms. Here we report sequencing of genomes from three Brassicaceae species (Leavenworthia alabamica, Sisymbrium irio and Aethionema arabicum) and their joint analysis with six previously sequenced crucifer genomes. Conservation across orthologous bases suggests that at least 17% of the Arabidopsis thaliana genome is under selection, with nearly one-quarter of the sequence under selection lying outside of coding regions. Much of this sequence can be localized to approximately 90,000 conserved noncoding sequences (CNSs) that show evidence of transcriptional and post-transcriptional regulation. Population genomics analyses of two crucifer species, A. thaliana and Capsella grandiflora, confirm that most of the identified CNSs are evolving under medium to strong purifying selection. Overall, these CNSs highlight both similarities and several key differences between the regulatory DNA of plants and other species.
Abstract 4424: Molecular mechanism study of a novel microtubule-binding agent-induced mitotic cell death of human hepatocellular carcinoma
Authors: Jun Jen Liu, Chun Te Ho, Li Xi Yang, Yu Jia Chang, Tsan Zon Liu, Po- Li Wei
Journal: Cancer Research (2010)

Abstract Polymerization and de-polymerization of microtubule are responsible for separation of chromosomes during cell division which has been considered to be one of major targets in cancer chemotherapy. In order to develop a newer generation of chemotherapeutic agents with higher efficacy and lower toxicity, a novel microtubule-binding agent (AD1), an analog of thiocolchicine, has been successfully synthesized. We here demonstrated AD1 could effectively kill a panel of seven human hepatocellular carcinoma (HCC) cell lines with varying degrees of differentiation. The IC50 values for all these HCC cell lines, using NCI standard protocol (sulforhodamine B, SRB), ranged from 2 to 50 nM. Cell cycle analysis study by flowcytometer unveiled that AD1 could evoke a dose-dependent cell cycle arrest in the G2/M phase. Further immunoflurorescence studies revealed that AD1 could also disrupt tubulin polymerization which would be responsible for the G2/M arrest. These prominent events provoked the disruption of cellular microtubule networks and prevented the proper formation of spindle apparatus and consequently resulted in the mitotic cell death. Interestingly, we also observed that AD1 could induce transcription factor ATF6 cleavage and subsequent reduction of the level of ER stress chaperone protein Grp78, and phosphorylated Akt expression. In vivo toxicity studies demonstrated that AD1, with maximum tolerance dose (MTD) of 150 mg/kg, was remarkably less toxic to normal C3H/HeN mice than colchicine (MTD of 1.6 mg/kg). The in vivo efficacy study of AD1 on HCC xenografts are now being investigated in nude mouse model in our laboratories. 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 4424.
Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis.
Authors: H W Murray, M J Oca, A M Granger, R D Schreiber
Journal: Journal of Clinical Investigation (1989)

Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-gamma or interleukin 2 alone. The absence of this T cell- and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.
Suppression of Ventricular Arrhythmias During Ischemia-Reperfusion by Agents Inhibiting Ins(1,4,5)P<sub>3</sub>Release
Authors: Xiao-Jun Du, Karen E. Anderson, Alexander Jacobsen, Elizabeth A. Woodcock, Anthony M. Dart
Journal: Circulation (1995)

Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate [Ins(1,4,5)P3]. The aim of this study was to test whether this increased Ins(1,4,5)P3 release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias.In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P3 were measured during early reperfusion. A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P3 release and the onset of VT and VF in parallel. A strong correlation existed between Ins(1,4,5)P3 content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF. In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo.Our results are consistent with the view that Ins(1,4,5)P3 release plays a pivotal role in mediating arrhythmias during early reperfusion. Agents inhibiting Ins(1,4,5)P3 release are antiarrhythmic and may have potential use clinically.
Circulating reticulin autoantibodies of IgA class in dermatitis herpetiformis
Authors: KERSTIN LJUNGHALL, ANNIKA SCHEYNIUS, URBAN FORSUM
Journal: British Journal of Dermatology (1979)

Circulating reticulin autoantibodies of IgA class and anti-nuclear antigen antibodies were found in a high frequency in dermatitis herpetiformis patients as compared with age- and sex-matched controls.
Familial atrioventricular heart block; an autosomal dominant trait.
Authors: M B Waxman, J D Catching, C H Felderhof, E Downar, M D Silver, M M Abbott
Journal: Circulation (1975)

A family of 28 individuals spanning four generations was investigated because of a finding of complete heart block in five members and the existence of a low degree of atrioventricular (A-V) heart block in a sixth member. The disorder was characterized by 1) adult onset in all, 2) complete A-V heart block in five and first degree A-V heart block in one, 3) sinus bradycardia in three, 4) atrial fibrillation in five, 5) abnormal QRS complex in five, 6) ventricular tachycardia in three, 7) left ventricular enlargement in all, and 8) mitral insufficiency in five. Proximal location of the A-V heart block was suggested by the fact that atropine caused acceleration of the ventricular rate and by the presence of a His bundle potential preceding the QRS complexes. Involvement of the distal conducting system was indicated by the widened QRS complex and a prolonged H-V interval. Pathologic examination in one case showed extensive sinus node fibrosis and interruption of the A-V node-His bundle connection. This disorder is probably due to an autosomal dominant trait.
Collection of unwanted drugs from private homes.
Authors: W. A. Nicholson
Journal: BMJ (1967)

It is not uncommon to find that the unused portions of medicines and tablets prescribed are left on shelves in private houses long after the need for them has ended.It was sus- pected that this stock might be quite large, and in March 1967 a week's collection was arranged in the Hartlepools, designed to fit in with the normal period of spring cleaning.The then TABLE I Tablets and capsules Ampoules .. Bottles of medicine Liniments .. Ointments and lotions Eye-drops and ointments 43,554 194 83 16 56 17 Ear-drops (bottles) Nasal drops (bottles) . .Lozenges Powders and cachets .. Pessaries and suppositories Miscellaneous ..
Correlates of Homosexual Behavior and the Incidence of Anal Cancer
Authors: Janet R. Daling, Noel S. Weiss, Larry L. Klopfenstein, Leah E. Cochran, Wong Ho Chow, Richard Daifuku
Journal: JAMA (1982)

To determine whether characteristics that are correlated with male homosexual behavior are associated with the incidence of cancer, the names of persons with a diagnosis of cancer in western Washington during 1974 to 1979 were linked to those in the state syphlis registry. Eight of 47 men with anal cancer were found to have had a reactive FTA test result; the expected number, based on the proportion of reactive cases among men with other sites of cancer, was only 0.40. Among men with anal cancer identified through ten population-based cancer-reporting systems in the United States, 24.4% had never been married, compared with 7.8% of men with colon and rectal cancer. Neither of these relationships was observed for women with anal cancer. Because in men, but not in women, having had syphilis and being single are associated with the practice of anal intercourse, our data suggest that anal intercourse may be a risk factor for anal cancer.