tbuckley/cabot-search huggingface dataset:
Abstract 1400: Obesity induced leptin-notch signaling axis in breast cancer.
Authors: Monica Battle, Corey Gillespie, Tanisha McGlothen, Marta Torroella-Kouri, Ruben R. Gonzalez-Perez
Journal: Cancer Research (2013)

Abstract Obesity leads to increased leptin levels and signaling which has been linked to the growth of breast cancer (BC). We early identified leptin as an inducer of Notch in BC cells. However, whether leptin-induction of Notch is instrumental to the development of BC is unknown. Objective: Therefore, we examined the impact of obesity and inhibition of leptin signaling (via LPrA2 antagonist) on the growth of syngeneic E0771-derived BC and tumor expression of Notch in lean and obese mice and in E0771 cell cultures. Methods: C57BL/6J female mice were fed either high-fat diet (HFD, 60% Kcal from fat) or normal diet (10% Kcal from fat). Obesity was defined as BW ≥ 20% BW Lean-control at week 5. Lean and diet-induced-obesity (DIO) mice were orthotopically inoculated with mouse E0771 cells in the lower left region of the mammary pad. One week later the mice were treated with either (1) pegylated leptin peptide receptor antagonist 2, PEG-LPrA2 or (2) PEG-Scrambled peptide (as control; 50μl i.v. tail vein/ 0.1 mM) following the two-arm design: (a) one and (b) two doses/weekly. Treatment lasted for 4 weeks. Tumor onset and growth was determined overtime and expression of Notch, its ligands, and crosstalk factors were assessed using western blot, immunohistochemistry, and ELISA. Leptin's effects on Notch and crosstalk factors were also investigated in E0771 cell cultures. Results: Obesity induced E0771-BC onset and growth and, increased the expression of Notch in vivo. Inhibition of leptin signaling had a higher impact on DIO mice than in lean mice by delaying onset and reducing tumor growth and the expression of Notch. Therefore, high levels of leptin in DIO-mice played a positive role in tumorigenesis. Similarly, leptin induced and PEG-LPrA2 decreased Notch expression in E0771 cells in vitro. Present data further validate the idea that the consumption of a high-fat diet leads to early BC onset and growth, which was linked to the leptin-Notch axis. Our results reinforce the potential use of inhibition of leptin signaling as a novel approach to fight breast cancer, especially in obese patients showing higher levels of leptin and incidence of BC. Funding: This work was supported by NIH/NCI 5SC1CA138658-03 and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP), NIH/2G12RR003034-26; U54 MSM/TU/UAB Cancer Center Partnership; and 1R21CA153172-01A1 (to MTK). This research was also supported, in part, facilities and support services at Morehouse School of Medicine (NIH 1C06 RR18386). Citation Format: Monica Battle, Corey Gillespie, Tanisha McGlothen, Marta Torroella-Kouri, Ruben R. Gonzalez-Perez. Obesity induced leptin-notch signaling axis in breast cancer. [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 1400. doi:10.1158/1538-7445.AM2013-1400
Molecular epidemiology of hepatitis C virus genotypes and subtypes among injecting drug users in Hungary
Authors: B Tresó, M Takács, Á Dencs, M Dudás, A Pár, E Rusvai
Journal: Eurosurveillance (2013)

The aim of this study was to determine the geographical distribution of hepatitis C virus genotypes/subtypes among people who inject drugs (PWID) recruited at 22 needle exchange sites and drug outpatient services in all seven Planning and Statistical Regions of Hungary. Of 198 such PWID, 147 (74.2%), 45 (22.7%) and six (3.0%) carried genotype 1, 3 or 4, respectively, and 31 (72.1%) of the 43 genotype 1 sequences were of subtype 1a. Genotype 3 was significantly more prevalent in provincial towns than in the capital, Budapest. Injecting for a longer period and an older age both correlated with a higher prevalence of genotype 3, suggesting possible future changes in genotype distribution. The distributions of hepatitis C virus genotypes/ subtypes differed significantly between the tested PWID and the general population. The identification of genotype 3 reflected its worldwide occurrence among PWID. Our results underline the importance of genotyping before treatment, especially among people who have ever injected drugs in Hungary.
Abstract 2396: Function of HLTF in the development of colon cancer and in the maintenance of genomic stability
Authors: Sumit Sandhu, Xiaoli Wu, Sabine Mai, Hao Ding
Journal: Cancer Research (2011)

Abstract HLTF (Helicase like Transcription Factor) is a DNA helicase protein which is homologous to SNF/SWI family. It has also been shown to be a functional homolog of yeast rad5, required for the maintenance of genomic stability through the ubiquitination of proliferating cell nuclear antigen (PCNA). Although the physiologic role of HLTF is largely unknown, inactivation of HLTF by promoter methylation has been demonstrated in more than 40% human colon cancers. In this study, we have applied mouse transgenic approaches to determine whether loss of HLTF function could be important for colorectal carcinogenesis. HLTF knockout mice were created by the deletion of first 5 exons of HLTF genome. The complete loss of HLTF expression in these mice was confirmed by Northern blot and RT-PCR assays. HLTF knockout mice did not show any developmental defects within a 2-year observation, indicating that HLTF is dispensable for normal development, and loss of HLTF function alone is not sufficient to drive colon carcinogenesis. To determine whether loss of HLTF function could cooperate with other tumor suppressors in the formation of colon cancers, we have bred HLTF knockout mice with the mutant mice for p53 and Apc (adenomtous polyposis coli). In HLTF−/−/Apc+/− mice, the significantly increased formation of intestinal adenocarcinoma and colon cancers were observed. Although very few HLTF−/−/p53−/− mice developed colon cancers, these mice had increased incidence of lymphoma formation. This finding suggests that loss of HLTF function could not only promote colon cancer formation, but also for other types of tumor. Cytogenetic analysis of colon cancer cells derived from HLTF−/−Apc+/− mice demonstrated a high incidence of gross chromosomal instabilities, including Robertsonian fusions, fragments and aneuploidy. All these genetic alterations were not observed in the intestinal tumor cells from Apc+/−, implicating that loss of HLTF function could induce genomic instability which contributes to colorectal carcinogenesis. To further establish the role of HLTF in the maintenance of genomic stability, we have also derived HLTF deficient mouse embryonic stem (ES) cells, and demonstrated that HLTF−/− ES cells exhibited similar, but a milder genetic alterations as observed in HLTF deficient colon cancer cells. Taken together, our work provides direct genetic evidence that loss of HLTF function as observed in a majority of human colon cancers is able to promote colorectal carcinogenesis. This function could be mediated by the induced genomic instability. 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 2396. doi:10.1158/1538-7445.AM2011-2396
Prednisone and Aspirin in Women with Autoantibodies and Unexplained Recurrent Fetal Loss
Authors: Carl A. Laskin, Claire Bombardier, Mary E. Hannah, Fred P. Mandel, Knox Ritchie, Vern Farewell, Dan Farine, Karen Spitzer, Lynda Fielding, Christine A. Soloninka, Maria Yeung
Journal: New England Journal of Medicine (1997)

Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss.
SAFETY OF MITRAL VALVE REPLACEMENT IN SEVERE SYSTOLIC HEART FAILURE: FIRST INTRA-OPERATIVE EVALUATION OF LEFT VENTRICULAR CONTRACTILE PERFORMANCE DURING OFF-BYPASS, TRANSCATHETER MITRAL VALVE REPLACEMENT
Authors: Mayooran Namasivayam, Michael Feneley, Christopher Hayward, Martin Shaw, Sriram Rao, Paul Jansz, David Muller
Journal: Journal of the American College of Cardiology (2016)
DNA and Destiny: Nature and Nurture in Human Behavior, by R Grant Steen /Plenum Press, 21, pp 295
Authors: S. W G Derbyshire
Journal: BMJ (1997)

R Grant Steen /Plenum Press, £21, pp 295 / ISBN 0 306 45260 X

My outspoken opinion that there is nothing within human biology that can predict behaviour resulted last year in a request for a book chapter. Having now looked at the issue in detail, I face an irritating fact: the data will not square with my opinion. DNA and Destiny adds insult to injury. The book is a wonderful exposition of the most recent and compelling evidence that genetic inheritance can predict future disease and future behaviour.

Steen makes excellent use of adoption data to make his points. For example, adopted children whose biological parents have a high IQ will average 16 IQ points more than their adoptive siblings born of a low …
Euthanasia and Nursing Practice — Right Question, Wrong Answer
Authors: Colleen Scanlon
Journal: New England Journal of Medicine (1996)

Public and professional sentiment about assisted suicide and euthanasia has led to intense debate, controversy, and confusion. In an era of unprecedented technological progress and postponement of death, considering actions to precipitate death seems almost counterintuitive. Yet it is increasingly apparent that medical advances have not necessarily fostered human dignity, quality of life, personal control, or appropriate care. The increasingly common assertion of a right to determine the time and manner of death — embodied in numerous legislative initiatives and court decisions — should serve as a wake-up call to health care providers. It represents not only the ultimate claim . . .
Multifocal Brucellosis Spondylodiscitis
Authors: MUNA MOHAMMED YOUSEF BAQER, MOHAMMED A.F. QURTOM, JAWAHER ABDULHADI ALI AL-AJMI, B. DAVID COLLIER, ABDELHAMID H. ELGAZZAR
Journal: Clinical Nuclear Medicine (2002)

MOHAMMED YOUSEF BAQER, MUNA M.D.; QURTOM, MOHAMMED A.F. M.D.; ABDULHADI ALI AL-AJMI, JAWAHER M.D.; COLLIER, B. DAVID M.D.; ELGAZZAR, ABDELHAMID H. M.D. Author Information
PTH-051 The First Years Outcome Data From Ibd-sshamp; Uk’s First Remote Web-based Self Management Programme For Stable Inflammatory Bowel Disease Patients
Authors: MW Johnson, K Lithgo, T Price
Journal: Gut (2014)

<h3>Introduction</h3> In February 2012 the Luton and Dunstable University Hospital, became the first hospital in UK to use a remote (web-based) programme to help manage stable inflammatory bowel disease (IBD) patients. IBD-SSHAMP (Supported, Self Help And Management Programme) aimed to transfer the care of stable IBD patients from hospital based outpatient appointments (OPAs), to effective community based monitoring + management, co-ordinated by specialist IBD nurses. <h3>Objective</h3> To improve cost efficiency by reducing the number of unnecessary routine OPAs + thereby improve OPA waiting times. <h3>Methods</h3> The LandD manages 2420 active IBD patients, most of which are seen twice a year in routine OPAs. 26 lack mental capacity and 117 do not have internet access. Using Patient Knows Best we developed individualised websites for all of our IBD patients, to offer them a direct communication portal and a symptomatic assessment tool that provides appropriate management advice via a traffic light system. If a patient scores badly, an alert is sent out to the specialist team. The websites have a library of self help advice sheets and upload the patients hospital results in graphical form. The system can be converted into 6 different languages and has both iPhone or Android apps. Patients can access this service from the comfort of their own homes or (like a health passport) whilst on the move/abroad. A proportion of our more stable patients can be transferred to community based care via IBD-SSHAMP and receive twice yearly virtual (telephone) clinics with blood and faecal (calprotectin) inflammatory marker assessments. By freeing up OPA space we can accommodate emergency patients usually within 24–48 hrs. <h3>Results</h3> We are steadily inviting the 2,277 IBD patients who have internet access to a personalised website, and have successfully transferred 420 onto IBD-SSHAMP. We plan to transfer a further 400 to community based IBD-SSHAMP by the end of 2014. Confidence is such that this second wave will primarily contain patients stable on immunosuppressants eg. azathioprine. So far IBD-SSHAMP has saved our CCG approx £68,000 (400 × 2 x £85), whilst reducing our OPA waiting times. Only 7 of our IBD-SSHAMP patients have required an emergency hospital OPA. We have received positive feedback from the patients, who feel more supported and appreciate that they are not being discharged. <h3>Conclusion</h3> IBD-SSHAMP is the UK's first internet based remote management system for managing stable IBD patients. This proof of concept project, has proven to be effective, safe and cost efficient. Our CCG have fully supported the concept and outcome, funding 2 additional IBD nurses to support the system. The Regional CCG are now keen to roll this concept out through the East of England. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3832: Defining molecular mechanisms controlling FES activation and microtubule binding as a potential strategy to limit mast cell recruitment to tumors via the SCF/KIT axis
Authors: Ester Kwok, John Allingham, Andrew W. B. Craig
Journal: Cancer Research (2011)

Abstract FES protein-tyrosine kinase (PTK) is activated downstream of the KIT receptor in mast cells, and promotes mast cell migration towards Stem cell factor (SCF), the ligand for KIT. Recently, tumor-derived SCF has been implicated in promoting mast cell recruitment leading to increased tumor vascularity and poor prognosis. FES is also a potential therapeutic target in leukemias driven by oncogenic KIT receptors that are constitutively active. Thus, defining FES activation and signaling mechanisms could lead to development of FES inhibitors as potential therapeutics in mast cell-involved tumors or KIT-driven leukemias. FES was previously shown to phosphorylate Tubulin, and localize to microtubules (MTs) in an SH2 domain-dependent manner. We hypothesized that defects in MT reorganization in FES-deficient mast cells may account for the observed defects in migration towards SCF. To map potential MT binding site(s) in FES, we performed MT binding assays, and identified two modes of FES binding, one via the N-terminal F-BAR/FX domains, and also via the SH2 domain. Interestingly, mutations predicted to disrupt oligomerization of the F-BAR/FX domains enhanced MT binding in vitro, and MT localization in vivo. Using in vitro kinase assays, we show that FES preferentially phosphorylates soluble tubulin compared to MTs, suggesting that FES recruitment to MTs may depend on their phosphorylation by other PTKs (such as Src family PTKs). In mast cells treated with SCF, FES co-localizes with MTs, including some localization to the MT organizing center (MTOC). We are currently comparing MTOC orientation in polarized wild-type and FES-deficient mast cells, and examining MT subsets marked by γ-tubulin, acetylation, and detyrosination. In conclusion, we find that FES interacts directly with MTs in vitro, and co-localizes with MTs in vivo, and hypothesize that disruption of FES-MT interaction and/or activation will be relevant therapeutic targets to limit mast cell recruitment in solid tumors, and growth of KIT-driven leukemias. Funded by an operating grant from Canadian Institutes for Health Research (MOP82882) to AWBC. 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 3832. doi:10.1158/1538-7445.AM2011-3832
Abstract 1927: Polyploidy across breast cancer subtypes.
Authors: Amy Fothergill, Mark Burkard
Journal: Cancer Research (2013)

Abstract Introduction: Breast cancer remains the most common cancer in women. Although treatment advances have improved the prognosis for many women, many existing therapies have significant associated toxicities. A major goal of current research is to develop targeted therapies based on characteristics of each individual's cancer. Polyploidy can provide a potential difference between cancer and normal cells that can be harnessed to selectively destroy cancer cells. We hypothesize that polyploidy is common in aggressive triple negative breast cancer. If this is the case, polyploidy could provide a target for therapy in triple negative cancers. Methods:We conducted a retrospective review of data collected by the University of Wisconsin Tumor Registry and HER2 testing by the state lab of hygiene between 2003 and 2011. Patients from the two data sets were matched by name and/or medical record number. Tumors were considered polyploid if ≥3 CEP17 signals were detected. Chi square testing and student T-tests were used to identify statistical correlations. Results: A total of 1211 were identified meeting eligibility criteria and 170 women had polyploid tumors. Of these, 72 had unknown or equivocal results for ER/PR or HER2 and were excluded from analyses. Polyploid tumors correlated with TNBC (p=0.028) and hormone receptor negative cancer (p=0.02). Subgroup analysis showed a positive correlation between HER2 positive tumors and polyploid tumors (p=0.0005). Polyploidy tumors were more likely to be either stage I or stage IV (p=0.0019). Vital status at last contact and age at diagnosis were not significantly different between the two groups (p=0.2875 and 0.7826, respectively). Discussion:We conclude that polyploid tumors cross all known subtypes of breast cancer, but are enriched among triple negative cancers. This may represent a viable group of cancers that can be targeted with specialized therapy. Table 1 Polyploid Euploid P HER2- 122 857 0.0005 Hormone- 38 164 0.02 Triple negative cancers 29 121 0.028 Stage I 80 612 0.002 Stage II 54 275 Stage III 29 99 Stage IV 4 49 Unknown stage 3 6 Mortality 33 168 0.29 Mean Age 59 58 0.78 Citation Format: Amy Fothergill, Mark Burkard. Polyploidy across breast cancer subtypes. [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 1927. doi:10.1158/1538-7445.AM2013-1927
Drug approval packages and briefing documents are already freely available
Authors: L. D. Sasich, E. Abi-Jaoude
Journal: BMJ (2013)

Goldacre lists four levels of clinical trial transparency, three of which are priorities for the AllTrials campaign.1 The first three of these priorities have been freely available for years for drugs approved or discussed by advisory committees in the US, yet these documents are rarely used.

These documents are prepared by scientists from the US Food and …
Tacrine as a Treatment for Alzheimer's Dementia
Authors: William K. Summers, Lawrence V. Majovski, Gary M. Marsh, Kenneth Tachiki, Arthur Kling
Journal: New England Journal of Medicine (1991)

To the Editor: The statement from the FDA's divisions of drug evaluation and research is curious. What this statement omits is noteworthy. The intense 3 1/2-year investigation of our data by a compliance division of the FDA did not abrogate any of our conclusions. The division did ask that we clarify some points concerning our original paper. This we did in an 851-word letter, which was edited by the compliance division of the FDA and then forwarded, in April 1989, to the Journal. The letter was never published. The FDA also asked that we restate our research plan. We . . .
Oxygen Toxicity in Man
Authors: Morley M. Singer, Frederick Wright, Loren K. Stanley, Benson B. Roe, William K. Hamilton
Journal: New England Journal of Medicine (1970)

Alternate patients (from a group of 40) after cardiac surgery received ventilation with pure oxygen, or the minimal inspired oxygen concentration required to maintain an arterial oxygen tension between 80 and 120 mm of mercury. The latter group of 20 patients did not receive more than 42 per cent inspired oxygen, and their mean duration of exposure was 21 hours, with a maximum of 44 hours. The mean exposure of 18 patients inspiring pure oxygen was 24 hours, with a maximum of 48 hours. No difference in intrapulmonary shunt, effective compliance, ratio of dead space to tidal volume or clinical course could be detected between the two groups. Of two additional patients who inspired pure oxygen for a prolonged period, one died of massive pulmonary hemorrhage related to clotting deficit after seven days' exposure, and the other recovered after five days' exposure. Fear of pulmonary oxygen toxicity should not prevent use of elevated inspired oxygen concentrations in critically ill patients requiring artificial ventilation. Further prospective studies are required to define the pulmonary effects of pure oxygen in such cases.