tbuckley/cabot-search huggingface dataset:
Abstract 5747: Elucidating the mechanisms by which Snail transcription factor promotes resistance to chemotherapy in breast carcinomas
Authors: Bethany N. Smith, Peri Nagappan, Mahandranauth Chetram, Latonia Taliaferro-Smith, Tamar Saintil, Clayton Yates, Cimona Hinton, Valerie Odero-Marah
Journal: Cancer Research (2012)

Abstract Snail (Snail1) is a zinc finger transcription factor that can induce EMT and is expressed at high levels in tumors. Maspin is a potential tumor suppressor, whose expression is lost as breast and prostate tumors progress during EMT. Maspin can be transcriptionally repressed by androgen receptor (AR) in prostate cancer cells. We hypothesized that overexpression of Snail will inhibit maspin expression and confer resistance to chemotherapy. Initially, we examined the expression of Snail and maspin in a panel of breast epithelial and breast cancer cells by RT-PCR and Western blot analysis. Preliminary results suggest that breast cancer cells express variable levels of Snail that is higher in breast cancer cells than in the normal MCF10A cells. We then utilized MCF-7 cells transfected stably with an empty Neo vector (MCF-7 Neo) or constitutively active Snail cDNA (MCF-7 Snail) that have been shown previously to represent an EMT model, and examined maspin, estrogen receptor alpha (ER-α) and AR levels by western blot analysis. MCF-7 Snail cells had upregulated levels of Snail and lower levels of maspin, ER-α and AR, as compared to MCF-7 Neo. MCF-7 Neo and MCF-7 Snail cells were also xenografted into nude mice and tissue sections stained immunohistochemically for Snail, maspin, and ER-α. Tumor volumes of MCF-7 Snail tumor xenografts were significantly larger than the MCF-7 Neo xenografts. MCF-7 Snail tissue sections expressed higher levels of Snail and lower levels of maspin and ER-α as compared to MCF-7 Neo sections. MCF-7 Neo and MCF-7 Snail cells were also treated with estradiol (E2, 0.01uM), tamoxifen (TAM, 10uM), and docetaxel (DOX, 1uM) individually; and in combination with E2 plus TAM and TAM plus DOX for periods of 24h and 72h to analyze changes in cell morphology and EMT marker expression. No effect on cell morphology or cell death was observed in MCF-7 Snail cells after TAM treatments, whereas TAM induced cell death in MCF-7 Neo. Expression of Snail was increased with E2 treatments and decreased with TAM, DOX, and combination treatments in MCF-7 Neo and MCF-7 Snail. AR expression decreased further in MCF-7 Snail cells and MCF-7 Neo following treatments with TAM and DOX. Overall, the Snail overexpression appears to promote resistance to TAM and DOX chemotherapeutic agents. The mechanism of Snail-regulated EMT needs to be investigated further to determine changes in breast cancer progression. 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 5747. doi:1538-7445.AM2012-5747
Following Dr Who to Oldbury power station
Authors: C. Harris
Journal: BMJ (1987)

With the mass arrival from the BMA's annual meeting of 150 potential converts to the cause of  power the Central Electricity Board's welcoming staff at Oldbury power station near Bristol must have felt a bit like Billy Graham. Certainly, every effort had been made to make us feel welcome and safe, with the tour of the station preceeded by a marquee buffet lunch, intended, perhaps, to encourage a receptive audience. Safety was the key preoccupation on the site. Ubiquitous posters exhorted em? ployees to Be wise?protect your eyes and to take care when lifting. As well as numerous notices about health and safety at work radiation detectors were evident everywhere. Information leaflets had been supplied on the coach so we had been able to fathom the basic concepts of reactor function but without some half remembered A level physics I would not have been able to digest all the facts about  fission. Fortunately, the guides make the entire process seem beautiful in its simplicity. Our impromptu lecture theatre was directly over the reactor and a small area of flooring had been removed so that we could view the core. It was quite eerie sitting on top of a working reactor, its steady hum forming a background to the talks, which opened with Professor T R Lee, professor of psychology at the University of Surrey, speaking on nuclear power as an emotional Stressor. He told us that visits were almost the only established method of changing people's attitudes on  power, mainly because for most of us objections to  power were based on emotional rather than intellectual arguments. Probability risk assessors use fatal accident frequency rates when comparing the risk associated with specific occupations. Using such data,  power was, he claimed, the safest form of power in Britain. Professor Lee also contrasted the industry's record with another seemingly low risk activity, horse riding. Yet from 1981 to 1983, 47 people had been killed in riding accidents and between 2000 and 3000 children had sustained riding accidents. Also, he questioned, if  power was deemed unsafe was conventional power any safer? One hundred and seventy nine people had died and 2676 had been seriously injured in coal mining between 1971 and 1982. Factors causing fear
Measuring performance and missing the point?
Authors: Iona Heath, Julia Hippisley-Cox, Liam Smeeth
Journal: BMJ (2007)

Targets do not necessarily translate into improvements for service users. <b>Iona Heath, Julia Hippisley-Cox, </b>and<b> Liam Smeeth </b>argue that performance measurement in the UK is shifting focus from what each patient needs and those who need it most
Abstract 1546: Effective co-targeting of tumor and tumor stroma for head and neck cancer treatment: making the right combination
Authors: Rosie Hongmei Xing, Yongfei Wu, Qingbei Zhang, Yong Huang, Jikun Shen, Hanli Fan, Jianrong Li, Hongyan Xiao, Younghee Lee, Ralph Weichselbaum, Mark Lingen, Yves A. Lussier
Journal: Cancer Research (2010)

Abstract Successful cancer management has been hindered by the development of inherent or acquired resistance. Increasing evidence suggest that manifestation of comparable resistance phenotype may arise from different combinations of molecular lesions. Signal transduction pathways in cancer cells exhibit remarkable flexibility for re-wiring such that cancer cells of solid tumors are able of altering the targeting receptor tyrosine kinases (RTKs) such as EGFR, or using unaffected and co-expressed RTKs signaling, or manifesting gain-of-function changes of the downstream signaling molecules to sustain tumor growth and progression. However, The potential of a “pathway rewiring” strategy to more efficiently target a deregulated signaling network has not been effectively explored due to the lack of scientific framework. Furthermore, the effort of developing effective agents or combinations that can effectively co-target both cancer cells and tumor stroma is lagging behind the therapeutic development aiming at cancer cell targeting. In this report, we demonstrate the effectiveness of integrating predicative pathway analysis to identify mTOR as a key interacting signaling target for developing a rational “pathway-based” combination to overcome resistance to anti-EGFR therapies in squamous carcinoma of the head and neck (HNC). We show for the first time that HNC cancer cells can effectively exploit the molecular interactions between EGFR and mTOR to confer reciprocal resistance. In addition, network modeling and comparison of xenograft with human tumor specimens identifies the abundant presence of myofibroblasts specifically associated with cancer state. We subsequently show the dependence of the clonogenic survival of myofibroblast cells on mTOR signaling in vitro. In vivo, only concomitant inhibition of EGFR and mTOR signaling via erlotinib and rapamycin, respectively, achieves effective differential and co-targeting of cancer cells and myofibroblast and endothelial cell functions in tumor stroma, leading to tumor regression. Thus, we show a systems’ approach-guided biological investigation has the potential to identify resistance mechanisms that can be explored to design more effective combinations of targeted therapies capable of overcoming resistance via “pathway rewiring” and achieving tumor-tumor stroma co-targeting. Based on these observations, an NIH funded network Phase II human clinical trial, lead by the University of Chicago Cancer Center, is soon underway to evaluate the therapeutic efficacy of this combination therapy. 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 1546.
Pretranscriptional Regulation of Tgf-β1 by PI Polyamide Prevents Scarring and Accelerates Wound Healing of the Cornea After Exposure to Alkali
Authors: Min Chen, Hiroyuki Matsuda, Linghua Wang, Takayoshi Watanabe, Makoto T Kimura, Jun Igarashi, Xiaofei Wang, Tohru Sakimoto, Noboru Fukuda, Mitsuru Sawa, Hiroki Nagase
Journal: Molecular Therapy (2009)

Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-β1 is upregulated and involved in the response to corneal injury and the process of corneal stromal scarring. To develop an efficient compound to inhibit Tgf-β1 in the cornea, we designed GB1201, a pyrrole–imidazole (PI) polyamide targeting rat Tgf-β1 gene promoter to the activator protein-1 (AP-1) binding site. GB1201 showed a high binding affinity to the target DNA sequence in the gel mobility shift and Biacore assays. GB1201 significantly inhibited the rat Tgf-β1 gene promoter activity in HEK (human embryonic kidney) 293 cells in a concentration-dependent manner. Topically administrated GB1201 was distributed immediately to the nuclei of all cell layers of the cornea and remained for 24 hours. A corneal alkali burn model in rats was used to evaluate the therapeutic efficacy of GB1201. GB1201 suppressed the upregulation of Tgf-β1 in the burned cornea, both in the mRNA and protein levels. Moreover, daily treatment with GB1201 for a week significantly improved the corneal tissue wound healing, reduced corneal stromal scarring, and prevented corneal haze formation. Our data suggest that PI polyamide may open new opportunities for therapeutic intervention in the treatment of chemically burned corneas. Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-β1 is upregulated and involved in the response to corneal injury and the process of corneal stromal scarring. To develop an efficient compound to inhibit Tgf-β1 in the cornea, we designed GB1201, a pyrrole–imidazole (PI) polyamide targeting rat Tgf-β1 gene promoter to the activator protein-1 (AP-1) binding site. GB1201 showed a high binding affinity to the target DNA sequence in the gel mobility shift and Biacore assays. GB1201 significantly inhibited the rat Tgf-β1 gene promoter activity in HEK (human embryonic kidney) 293 cells in a concentration-dependent manner. Topically administrated GB1201 was distributed immediately to the nuclei of all cell layers of the cornea and remained for 24 hours. A corneal alkali burn model in rats was used to evaluate the therapeutic efficacy of GB1201. GB1201 suppressed the upregulation of Tgf-β1 in the burned cornea, both in the mRNA and protein levels. Moreover, daily treatment with GB1201 for a week significantly improved the corneal tissue wound healing, reduced corneal stromal scarring, and prevented corneal haze formation. Our data suggest that PI polyamide may open new opportunities for therapeutic intervention in the treatment of chemically burned corneas.
Clinical Recognition of Tricuspid Stenosis
Authors: JOSEPH K. PERLOFF, W. PROCTOR HARVEY
Journal: Circulation (1960)

Clinical criteria for the recognition of tricuspid stenosis were studied in 13 cases, all personally observed by the authors. The results suggest that application of these criteria not only allows a confident diagnosis of tricuspid stenosis in a substantial majority of cases, but also allows the lesion to be recognized relatively early in its natural history.
Intravenous administration of follistatin: Delivery to the liver and effect on liver regeneration after partial hepatectomy
Authors: K Kogure, Y Zhang, M Kanzaki, W Omata, T Mine, I Kojima
Journal: Hepatology (1996)

When 1 μg 125I–follistatin was administered into a rat intravenously, radioactivity levels in serum decreased rapidly. Analysis with a biexponential equation showed that the initial half– life and the terminal half–life were 4.0 and 130.8 minutes, respectively. After 2 hours of infusion, approximately 9% of the follistatin infused remained in the liver, which was much more than that in kidney, spleen, pancreas, intestine, or lung. Autoradiography of the liver obtained at 24 hours of infusion revealed that numerous grains were located in parenchymal cells. Radioactivity of 125I– follistatin in the liver remained elevated until 72 hours and declined markedly thereafter. When a booster shot of 125I–follistatin was administered at 72 hours, radioactivity in the liver at 120 hours was markedly increased compared with that in rats that received a single shot of 125I–follistatin. We then examined the effect of intravenous infusion of follistatin on liver regeneration after hepatectomy of 70%. Immediately after the hepatectomy, either 1 microgram follistatin or saline was infused intravenously. In some rats, a booster shot was infused at 72 hours. After 120 hours of hepatectomy of 70%, remnant liver weight, liver regeneration rate, and DNA content were significantly ( P &lt; .05) higher in rats that received a booster shot of follistatin at 72 hours than those in control rats. These results indicate that follistatin administered intravenously accumulates in the liver and promotes liver regeneration after partial hepatectomy.
CALCIUM AND PHOSPHORUS METABOLISM IN OSTEOMALACIA. V. THE EFFECT OF VARYING LEVELS AND RATIOS OF CALCIUM TO PHOSPHORUS INTAKE ON THEIR SERUM LEVELS, PATHS OF EXCRETION AND BALANCES, IN THE PRESENCE OF CONTINUOUS VITAMIN D THERAPY
Authors: S. H. Liu, C. C. Su, S. K. Chou, H. I. Chu, C. W. Wang, K. P. Chang
Journal: Journal of Clinical Investigation (1937)
Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells
Authors: R Klar, S Schober, M Rami, S Mall, J Merl, S M Hauck, M Ueffing, A Admon, J Slotta-Huspenina, M Schwaiger, S Stevanović, R A J Oostendorp, D H Busch, C Peschel, A M Krackhardt
Journal: Leukemia (2014)
Consent and confidentiality in teaching in general practice: survey of patients' views on presence of students
Authors: N. O'Flynn, J. Spencer, R. Jones
Journal: BMJ (1997)

Medical schools are expanding their teaching in general practices,1 2 but there are few studies on patients' responses to the presence of medical students at consultations with general practitioners. In 1974 Wright reported that up to 40% of patients in one practice preferred not to discuss personal anxieties, family problems, or sexual problems in the presence of a student.3 Seabrook and Evans discussed general practice teaching with patients and carers.4 Patients expressed concern about whether they would be given a choice about a student being present and reported bad experiences of hospital teaching. Most recently, Cooke et al concluded from a questionnaire survey that only 3% of patients had negative views about the presence of a student.5 We report patients' views about consent and confidentiality using a questionnaire developed from semistructured interviews.

The questionnaire had four …
New European rules require all herbal medicines to be registered
Authors: R. Watson
Journal: BMJ (2011)

Up to $500m a year could be put to better use by stopping ineffective and potentially harmful supplementation programmes in poorer countries, say <b>JB Mason</b>, <b>CS Benn</b>, and <b>HPS Sachdev</b>; but <b>Keith P West Jr</b>, <b>Amanda C Palmer,</b> and <b>Alfred Sommer</b> disagree, saying that such programmes have been proved to save millions of lives and should be withdrawn only when robust evidence permits
Echocardiographic Detection of Left Atrial Extension of Bronchial Carcinoma
Authors: Aleksandar D. Popovic
Journal: JAMA (1989)

IT IS well known from autopsy series that metastatic tumors of the heart can be found in 1.5% to 20.6% (average, 6%) of patients with malignancies.<sup>1</sup>The most common cause of metastatic heart disease is bronchial carcinoma, followed by carcinoma of the breast, malignant melanoma, lymphoma, and leukemia, in decreasing order of frequency.<sup>1</sup>However, cardiac invasion is infrequently diagnosed ante mortem due to the lack of specific clinical manifestations.<sup>2</sup> Atrial extension has been reported as a common route of local spread in patients with bronchial carcinoma.<sup>3,4</sup>The echocardiographic features of such extension have been illustrated in only two cases,<sup>5,6</sup>to our knowledge. The purpose of this report is to describe three patients with bronchial carcinoma in whom left atrial extension of the tumor was diagnosed by two-dimensional echocardiography. <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> An 80-year-old man had a history of long-standing murmur consistent with aortic
Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial)
Authors: Qin Ning, Meifang Han, Yongtao Sun, Jiaji Jiang, Deming Tan, Jinlin Hou, Hong Tang, Jifang Sheng, Mianzhi Zhao
Journal: Journal of Hepatology (2014)
Low Dose Vincristine Therapy of Reticulum Cell Sarcoma.
Authors: Harvey E. Finkel
Journal: Annals of Internal Medicine (1966)

s1 May 1966Low Dose Vincristine Therapy of Reticulum Cell Sarcoma.Harvey E. Finkel, M.D. (Associate), William J. Yount, M.D.Harvey E. Finkel, M.D. (Associate)Search for more papers by this author, William J. Yount, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1164_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAmong malignant lymphoreticular tumors, reticulum cell sarcoma is the least responsive to therapy. The course of this disease is usually one of inexorable progression. Alkylating agents, vinblastine, and irradiation have been used extensively; however responses are not frequent, and are often incomplete and transient.Vincristine is known to possess activity against reticulum cell sarcoma; unfortunately treatment must often be stopped because of neurotoxicity. In an attempt to avoid severe toxicity while maintaining good therapeutic responses, we have used vincristine in small doses (as low as 5 µg/kg biweekly).Six patients with histologically confirmed, far advanced disease and resistance to other... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Harvey E. Finkel, M.D. (Associate); William J. Yount, M.D.Affiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1164-1164KeywordsMalignant tumorsSarcomaToxicity ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Searching for the Yeast Connection
Authors: John E. Bennett
Journal: New England Journal of Medicine (1990)

Few illnesses have sparked as much hostility between the medical community and a segment of the lay public as the chronic candidiasis syndrome. Those who argue for the existence of this complex of symptoms (also known as polysystemic candidiasis and the candidiasis hypersensitivity syndrome) have leveled a serious charge against the medical community, claiming that it is not fulfilling one of its most important obligations to its patients. The charge is simply put: You physicians are not listening to your patients. Physicians are considered to have failed to hear and believe their patients when they say they are unwell, because . . .
Membrane-bound lactoferrin alters the surface properties of polymorphonuclear leukocytes.
Authors: L A Boxer, R A Haak, H H Yang, J B Wolach, J A Whitcomb, C J Butterick, R L Baehner
Journal: Journal of Clinical Investigation (1982)

Polymorphonuclear leukocytes (PMN) aggregate and avidly attach to endothelium in response to chemotactic agents. This response may be related in part to the release of the specific granule constituent lactoferrin (LF). We found by using immunohistology and biochemical and biophysical techniques that LF binds to the membrane and alters the surface properties of the PMN. Upon exposure of PMN treated with 5 micrograms/ml cytochalasin B to 2 x 10(-7) M formyl-methionine-leucine-phenylalanine for 5 min, the PMN mobilized LF to their surface as observed by immunoperoxidase staining for LF. At added LF levels ranging from 4 to 15 micrograms/10(7) PMN there was a dose-dependent reduction in PMN surface charge reaching 4 mV, when the partitioning into the membrane of a charged amphipathic nitroxide spin label was measured by electron spin resonance spectroscopy, whereas transferrin was without effect. When 125I-FeLF was added to human PMN in increasing amounts and the results corrected for the residual amount of free LF contaminating the cells, the PMN were saturated with LF at concentrations between 100 and 200 nM in the medium. Human PMN bound 1.35 x 10(6) molecules per cell and the calculated value for the association constant for these receptors was 5.2 x 10(6) M-1. Additionally, 6 micrograms/ml LF served as an opsonin for rabbit MN to promote PMN uptake by rabbit macrophages, when assessed by electron microscopy, but lysozyme did not. These studies indicate that LF can bind to the surface of the PMN and reduce its surface charge. This correlates with enhanced "stickiness" leading to a variety of cell-cell interactions.
War Atrocities in Vietnam
Authors: Hugh H. Hussey
Journal: JAMA (1974)

From the time of recorded history, wars have had their share of atrocities. Never before, however, have United States military engagements received such publicity about atrocities committed by our troops during the long campaign in Vietnam. Although the heavy bombings by US forces undoubtedly took their toll of innocents, such acts were impersonal when compared to an incident like the one at My Lai. In the current issue of<i>Archives of General Psychiatry</i>(30:191-196, 1974) Haley reports her experience, beginning in 1969, of evaluating 130 Vietnam-duty veterans for psychotherapy. Forty of the men reported responsibility for atrocious acts, ranging from those provoked during the intensity of combat to sadistic brutality unrelated to any immediate external threat. She makes a sharp distinction between the psychological effects on men guilty of atrocities and the depression that characterized the traumatic war neurosis observed in veterans of World War II and the Korean conflict.