tbuckley/cabot-search huggingface dataset:
Abstract 4324: Loss of TGF-beta receptor I and PTEN promotes HNSCC
Authors: Yansong Bian, Bradford Hall, Zhi-Jun Sun, Alfredo Molinolo, Wanjun Chen, Carter Van Waes, Ashok Kulkarni
Journal: Cancer Research (2011)

Abstract The precise molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been clearly delineated. Here, we report that defects in the TGF-β and PI3K/Akt signaling pathways are common in human HNSCCs. Activation of the PI3K/Akt pathway due to PTEN deletion gives rise to hyperproliferation in the head and neck epithelia, but only a few lesions progressed to HNSCCs. Strikingly, PTEN deletion, in combination with a loss of Tgfbr1, caused HNSCC with complete penetrance. Molecular analysis revealed enhanced cell proliferation, increased expression of CCND1 and decreased expression of CDKN1A in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/PTEN double conditional knockout (2cKO) mice. These tumors displayed pathology and multiple molecular alterations that resembled human HNSCCs. Furthermore, the neoplastic transformation was due to senescence evasion and was associated with an increased number of putative (CD44+, CD133+) cancer stem cells. In addition, myeloid derived suppressor cell (MDSC) infiltration, angiogenesis and immune suppression in the tumor microenvironment also accompanied mouse head and neck carcinogenesis. The Tgfbr1/PTEN 2cKO mouse model is suitable for preclinical intervention and has significant implications in the development of diagnostic cancer biomarkers as well as effective preventive and therapeutic strategies for the treatment of HNSCCs. 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 4324. doi:10.1158/1538-7445.AM2011-4324
Mortality Patterns Among Chemical Plant Workers Exposed to Formaldehyde and Other Substances
Authors: G. M. Marsh, R. A. Stone, N. A. Esmen, V. L. Henderson
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Mortality Patterns Among Chemical Plant Workers Exposed to Formaldehyde and Other Substances Get access Gary M. Marsh, Gary M. Marsh Department of Biostatistics, University of PittsburghPittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Roslyn A. Stone, Roslyn A. Stone Department of Biostatistics, University of PittsburghPittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Nurtan A. Esmen, Nurtan A. Esmen Esmen Research and Engineering2531 Wickline Rd., Gibsonia. PA 15044. Search for other works by this author on: Oxford Academic PubMed Google Scholar Vivian L. Henderson Vivian L. Henderson * Department of Biostatistics, University of PittsburghPittsburgh, Pa. * Gary M. Marsh, ph.D., Rm. A410. Crabtree Hall, Graduate School of Public Health. University of Pittsburgh. Pittsburgh. PA 15261. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 5, 2 March 1994, Pages 384–386, https://doi.org/10.1093/jnci/86.5.384 Published: 02 March 1994 Article history Received: 23 July 1993 Revision received: 24 November 1993 Accepted: 02 December 1993 Published: 02 March 1994
AB0363 Rate of tuberculin skin test or interferon gamma release assay conversion during anti-tumor necrosis factor therapy in rheumatic patients
Authors: C. Hatzara, E. Hadziyannis, A. Kandili, S. Tsikrika, M. Minopetrou, G. Georgiopoulos, D. Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite negative baseline testing for tuberculosis (TB) with traditional (tuberculin skin test/TST, chest X-ray/CXR) or newer (interferon-gamma release assays/IGRAs) screening methods, a small number of patients receiving anti-tumor necrosis factor (TNF) therapies can develop TB during chronic treatment. The proportion of patients who display conversion of TB screening tests during therapy has not been adequately evaluated in prospective studies so far. <h3>Objectives</h3> We aimed at studying prospectively the rate of TB test conversion (TST, IGRAs) during anti-TNF therapy in patients with negative baseline screening. <h3>Methods</h3> Forty patients (mean age=46±14 years, females/males=23/17) with various rheumatic diseases (rheumatoid arthritis/RA =15, spondyloarthropathies/ SpA =24, other=1) and negative baseline TB screening (TST:&lt;5 mm, negative T.Spot®-TB and QuantiFERON®-TB Gold In Tube/QFT-GIT, negative CXR) were included. A year after anti-TNFa therapy (adalimumab: n=16, infliximab: n=13, etanercept: n=10, certolizumab: n=1) all patients underwent re-testing with TST, both IGRAs and CXR. <h3>Results</h3> Among the 40 patients enrolled, 13 patients (32.5%) demonstrated conversion of at least one screening assay. Fifteen percent showed conversion of TST (n=6), 10% of T.Spot®-TB (n=4) and 7.5% of QFT-GIT (n=3). Interestingly none of these patients showed concomitant conversion of ≥2 screening tests. No history of new M.Tb exposure or clinical and/or radiographic evidence of TB were noted. There were no significant difference in age, sex, disease diagnosis or duration, previous BCG vaccination, concomitant DMARD/steroid use or type of anti-TNFa treatment between those who converted (n=13) vs those who did not (n=27). <h3>Conclusions</h3> These preliminary data suggest that approximately 1/3 of patients develop conversion of at least one screening assay for TB one year after anti-TNFa therapy. It remains unclear if these test conversions are due to new or past non-diagnosed (reconstitution of impaired immune response against M.Tb antigens) M. TB exposure. The clinical significance of these findings and the need for LTBI therapy in this group remains to be elucidated. <h3>Disclosure of Interest</h3> None Declared
Time after Time — Health Policy Implications of a Three-Generation Case Study
Authors: Caroline Sayer, Thomas H. Lee
Journal: New England Journal of Medicine (2014)

Interview with Dr. Thomas Lee on the social factors that affect health and possible reforms that could help to address them. (09:10)Download A three-generation case study shows the intertwined effects of many negative social factors on the health of a family. Our ability as clinicians to change the overall trajectory of such patients' health issues through traditional medical means is limited at best.
Interference of cadmium with ATP-stimulated nuclear calcium uptake.
Authors: S Hechtenberg, D Beyersmann
Journal: Environmental Health Perspectives (1994)

The spatial and temporal regulation of intracellular free Ca2+ serves as a modulator of signal transduction pathways involved in cell growth and differentiation. Thus, interference of metals with intracellular Ca2+ homeostasis has been considered as a target of toxic action. We used the fluorescence indicator fura-2 to monitor the level of free Ca2+ in isolated bovine liver nuclei. Nuclei accumulated Ca2+ by an ATP-stimulated Ca2+ uptake system, which is sensitive to inhibition by thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases. Preincubation of nuclei with nanomolar concentrations of free Cd2+ resulted in a dose-dependent inhibition of ATP-dependent nuclear Ca2+ uptake. We conclude that impairment of nuclear Ca2+ regulation caused by Cd2+ provokes alterations in nuclear events related to gene expression and cell proliferation.
Abstract 2515: Anti- GP88 (progranulin) antibody to GP88 (progranulin) inhibits breast tumor growth and restores sensitivity to tamoxifen
Authors: Ginette Serrero, Jianping Dong, Jun Hayashi
Journal: Cancer Research (2012)

Abstract GP88 (Progranulin, PCDGF, acrogranin) is an 88 kDa glycoprotein that is the largest member of the granulin/epithelin family of growth modulators characterized by 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. Our laboratory demonstrated the role of GP88 as an autocrine growth and survival factor in breast cancer: 1) GP88 expression increases with tumorigenesis; 2) inhibition of GP88 expression by antisense transfection in MDA-MB-468 cells inhibited tumor formation in nude mice by 90%; 3) in ER+ breast cancer cells, GP88 stimulates proliferation and its overexpression confers estrogen independence; 4) GP88 is a strong survival factor that confers resistance to anti-estrogen and aromatase inhibitors in ER+ breast cancer; 5) GP88 is expressed in 80% invasive ductal carcinoma and 60% of ductal carcinoma whereas it is negative in benign lesions and normal mammary epithelial cells; 6) pathological studies with 530 cases of ER+ invasive ductal carcinoma showed that GP88 tumor expression is a prognostic indicator of recurrence in early stage breast cancer patients; 7) GP88 is secreted and can be detected in the serum of breast cancer patients at an increased level when compared to healthy subjects. Based on these results GP88 represents an ideal therapeutic and diagnostic target in breast cancer. We developed a neutralizing anti-GP88 antibody AG1. AG1 inhibits GP88 biological effect in a dose-dependent fashion. In the present study, we investigated the effect of AG1 on the tumor development of tamoxifen sensitive (MCF-7) and resistant (TamR) estrogen receptor positive breast cancer cells lines injected in nude mice. We show that AG1 alone (5mg/kg) inhibited tumor growth of MCF-7 cells injected into nude mice in a similar efficacy as tamoxifen. Interestingly, AG1 in combination with tamoxifen inhibited by more than 50% tumor formation of TamR cells, whereas tamoxifen only had no effect. These data suggest that inhibiting GP88 provide a novel and alternate pathway for restoration of tamoxifen sensitivity in ER+ breast cancer. This works is supported by grant 2R44CA124179 from the National Cancer Institute. 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 2515. doi:1538-7445.AM2012-2515
AB0102 Pycnogenol ameliorate collagen-induced arthritis through modulating inflammatory mediators, decreases oxidative stress, and improves clinical signs in wistar rats
Authors: S. Umar, S. Ahmad, C.K. Katiyar, H.A. Khan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads destruction of joints. Current treatment modalities for RA either produce symptomatic relief (NSAIDs) or modify the disease process (DMARDs)<sup>1</sup>. Though effective, their use is also limited by their side effects. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged<sup>2</sup>. <h3>Objectives</h3> To assess antioxidant and antiarthritic potential of a pycnogenol in collagen induced arthritis in Wistar rats. <h3>Methods</h3> Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Pycnogenol<sup>3.4</sup> was administered at dose of 20 mg kg<sup>-1</sup> body weight once daily for 21 days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1β, IL-6, TNF-α, IL-10, IFN-γ, and PGE<sub>2</sub>) and histological studies in joints. <h3>Results</h3> Pycnogenol was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied in treated rats as compared to RA rats. Oral administration of pycnogenol significantly reduced the levels of inflammatory mediators (IL-1β, IL-6, TNF-α, IFN-γ, and PGE<sub>2</sub>) and increase level of IL-10. The protective effects of pycnogenol against RA were also evident from the decrease in arthritis scoring and bone histology. <h3>Conclusions</h3> The fact that pycnogenol abolishes a number of factors known to be involved in RA. Therefore, this study indicates that the administration pycnogenol has significant potential in the treatments for chronic inflammatory diseases like rheumatoid arthritis as an alternative and safe therapy. <h3>References</h3> Koelink PJ, Overbeek SA, Braber S, de Kruijf P, Folkerts G, Smit MJ, et al. Targeting chemokine receptors in chronic inflammatory diseases: An extensive review. Pharmacol Ther. 2012 Jan;133(1):1-18. Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet. 2011 Jun 1;50(6):349-69. Khan MM, Hoda MN, Ishrat T, Ahmad A, Khan MB, Khuwaja G, Raza SS, Safhi MM, Islam F. Amelioration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced behavioural dysfunction and oxidative stress by Pycnogenol in mouse model of Parkinson's disease. Behav Pharmacol. 2010 Sep;21(5-6):563-71. Ince, O.Yesil-Celiktas, N.U.Karabay-Yavasoglu, G.Elgin Effects of Pinus brutia bark extract and Pycnogenols in a rat model of carrageenan induced inflammation. Phytomedicine 16 (2009) 1101–1104. <h3>Disclosure of Interest</h3> None Declared
Case 21-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely
Journal: New England Journal of Medicine (1990)

Presentation of Case A 21-year-old man was admitted to the hospital because of recurrent episodes of left-sided pneumonia, asthma, increasing dyspnea, and a productive cough. The patient was in a good state of health until 39 months earlier, when pneumonia developed and was treated on an outpatient basis with penicillin. Pneumonia recurred 30, 24, 15, and 12 months before entry; each episode was characterized by fever, purulent sputum, and dyspnea and was treated at home with penicillin, with subsidence of symptoms in approximately three weeks. Repeated x-ray films of the chest showed that the process was invariably left-sided. Two years . . .
Solitary Splenic Metastasis From Hepatocellular Carcinoma Detected on 18F-FDG PET/CT
Authors: Do-Hoon Kim, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Journal: Clinical Nuclear Medicine (2014)

We report a case of solitary splenic metastasis from hepatocellular carcinoma detected on F-FDG PET/CT. A 67-year-old man with hepatocellular carcinoma was referred for F-FDG PET/CT to determine the cause of his elevated serum α-fetoprotein levels after liver segmentectomy and radio-frequency ablation. F-FDG PET/CT imaging showed focal FDG uptake in the spleen, with no other abnormal findings. A splenectomy was performed, and histopathologic examination confirmed the lesion as a metastasis from the hepatocellular carcinoma.
Atypical Sites of Bony Metastases in a Prostate Cancer Patient
Authors: Cyprian Świętaszczyk, Stanisław Pilecki, Krzysztof Łuka, Roman Junik
Journal: Clinical Nuclear Medicine (2011)

A 65-year-old patient with a newly diagnosed prostate cancer underwent planar bone scintigraphy. This study revealed increased focal activity in the right distal clavicle, left scapula, and right greater cornu of the hyoid bone. SPECT/CT confirmed these lesions. Metastases to the hyoid bone are rare.
Foundations of Cost-Effectiveness Analysis for Health and Medical Practices
Authors: Milton C. Weinstein, William B. Stason
Journal: New England Journal of Medicine (1977)

Abstract Limits on health-care resources mandate that resource-allocation decisions be guided by considerations of cost in relation to expected benefits. In cost-effectiveness analysis, the ratio of net health-care costs to net health benefits provides an index by which priorities may be set. Quality-of-life concerns, including both adverse and beneficial effects of therapy, may be incorporated in the calculation of health benefits as adjustments to life expectancy. The timing of future benefits and costs may be accounted for by the appropriate use of discounting. Current decisions must inevitably be based on imperfect information, but sensitivity analysis can increase the level of confidence in some decisions while suggesting areas where further research may be valuable in guiding others. Analyses should be adaptable to the needs of various health-care decision makers, including planners, administrators and providers. (N Engl J Med 296:716–721, 1977)
FEASIBILITY OF DIRECT AORTIC IMPLANTATION OF THE LOTUS VALVE: A MULTICENTER EXPERIENCE
Authors: Vinayak Nilkanth Bapat, Zhan Yun Lim, Mika Laine, Rudiger Lange, Sabine Bleiziffer, Uday Trivedi, David Hildick-Smith, Matthias Gotberg, Thomas Modine, Heyman Luckraz, Saib Khogali, Joachim Schofer, Dominic Allocco, Simon Redwood
Journal: Journal of the American College of Cardiology (2016)
A Prospective Randomized Trial Comparing a Virtual Reality Simulator to Bedside Teaching for Training in Sigmoidoscopy
Authors: L B Gerson, J Van Dam
Journal: Endoscopy (2003)

Clinical investigation using endoscopy simulators is now possible due to recent advances in virtual reality technology. A prospective randomized trial was conducted to compare the exclusive use of a virtual reality endoscopy simulator with bedside teaching for training in sigmoidoscopy.Internal medicine residents were randomly assigned to training exclusively using a virtual reality simulator (group 1) or via bedside teaching (group 2). Residents were then observed performing five sigmoidoscopic procedures in asymptomatic patients referred for colorectal cancer screening. Endoscopic examinations were evaluated for procedure duration, completion, ability to perform retroflexion, and level of patient comfort/discomfort. Each examination was scored from 1 (inability to insert the endoscope beyond the rectum) to 5 (able to complete the entire examination independently in less than 20 min).Sixty-six sigmoidoscopic examinations were completed by nine residents in group 1 (simulator-trained group) and seven residents in group 2 (traditional teaching group). Participants in group 1 had more difficulty with initial endoscope insertion and negotiation of the rectosigmoid junction (mean score +/- SEM 2.9 +/- 0.2) than those in group 2 (3.8 +/- 0.2) ( P < 0.001). The splenic flexure was reached independently in 10 of 34 examinations (29 %) in group 1, compared with 23 of 32 examinations (72 %) in group 2 ( P = 0.001). Retroflexion was successfully performed by 19 of 34 (56 %) in group 1 compared to 27 of 32 (84 %) in group 2 ( P = 0.02). The average procedure time, patient satisfaction, and discomfort associated with the procedure did not differ statistically between the two groups.The use of a state-of-the-art virtual reality-based endoscopy simulator is inferior to traditional bedside teaching techniques when used exclusively for training medical residents to perform sigmoidoscopy.
THE CORNELL PRODUCT IS A NOVEL ELECTROCARDIOGRAPHIC MARKER OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Eugene Tan, Siew Pang Chan, Chang Fen Xu, Jonathan Yap, Mark Richards, Lieng Ling, David Sim, Fazlur Jaufeerally, Poh Shuan Yeo, Seet Yoong Loh, Hean Yee Ong, Kui Toh Leong, Nyunt Shwe Zin, Liang Feng, Tze Pin Ng, Peter Okin, Carolyn Lam, Toon Wei Lim
Journal: Journal of the American College of Cardiology (2016)
Abstract 5667: Identification of chemopreventive agents against dibenzo[a,l]pyrene-induced DNA adducts and potential mechanisms
Authors: Gilandra K. Russell, Manicka V. Vadhanam, Ramesh C. Gupta
Journal: Cancer Research (2010)

Abstract Intervention with compounds of natural origin with little or no known toxicity is considered an effective means to prevent cancer development. We describe here a microsomal activation system in combination with 32P-postlabeling adduct assay to identify efficacious phytochemicals against the potent lung and breast carcinogen, dibenzo[a,l]pyrene (DBP). Briefly, salmon testes (st)-DNA was incubated with test agents (150 µM), DBP (10 µM), β-naphthoflavone-induced rat liver microsomes, co-factors in Tris. HCl (50 mM, pH 7.4). After incubation for 60 min at 37°C, the reaction was terminated. Analysis of the purified DNA by 32P-postlabeling showed essentially the same spectra of multiple adducts in all samples. However, quantitative differences were observed. Of nine phytochemicals tested, several compounds almost completely abolished the DNA adduct formation, some showed modest inhibition, while others were ineffective: resveratrol (95% reduction), delphinidin (94%), tanshinone I, (84%) tanshinone IIA (78%), diindolylmethane (73%), indole-3-carbinol (49%) and cyanidin (46%) and withaferin A (33%); cucurbitacin B showed insignificant reduction. All adducts were found to be equally inhibited, suggesting that activity of both CYP1A1 and 1B1, the major cytochromes P450s involved in the metabolism of DBP, were similarly affected. Oltipraz included as positive control, as expected, showed over 80-90% inhibition. To determine if the adduct inhibition occurred due to scavenging of electrophilic metabolites of DBP, st-DNA was incubated with the most effective test agents in the presence of anti-dibenzo[a,l]pyrene diolepoxide (anti-DBPDE). Analysis of the resultant adducts showed that only delphinidin, cyanidin and resveratrol showed modest inhibition (30-45%); other compounds were ineffective. Ellagic acid, which is known to scavenge the DBP electrophilic metabolite, almost completely abolished the adduct formation. Together, our data suggest that resveratrol, delphinidin, tanshinones and diindolylmethane are potent inhibitors of microsomal DBP-DNA adduct formation. While, the adduct inhibition for delphinidin and resveratrol may occur, in part, due to scavenging of the electrophilic metabolite of DBP, both these agents, tanshinones and diindolylmethane may also elicit their activity by inhibiting the cytochromes P450 activity. In summary, resveratrol, delphinidin, tanshinones and diindolylmethane, all of which are consumed either in fruits and vegetables or via folklore medicine (tanshinones) may be useful in the prevention of DBP-mediated lung and mammary tumorigenesis (Supported from the USPHS grants CA-118114, ES-011564 and Agnes Brown Duggan Endowment). 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 5667.