tbuckley/cabot-search huggingface dataset:
FRI0194 Treatment with anti-tumor necrosis factor (TNF) biologics to human t-lymphotropic virus type 1 (HTLV-1) positive patients with rheumatoid arthritis (RA): a case-control study
Authors: S. Miyauchi, K. Umekita, T. Hidaka, Y. Hashiba, T. Kawaguchi, M. Matsuda, K. Kubo, S. Ueno, N. Kusumoto, I. Takajo, Y. Kai, Y. Nagatomo, A. Okayama
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To see whether the clinical features and responses to anti-TNF of HTLV-1 positive patients with RA are different from those of HTLV-1 negative patients. <h3>Methods</h3> The clinical features and response to anti-TNF were compared between 10 female HTLV-1 positive RA patients and 20 age-matched female HTLV-1 negative patients, who were diagnosed based on the 1987 ACR criteria for RA. Therapeutics response was evaluated using the EULAR improvement criteria. <h3>Results</h3> Significantly higher baseline level of C-reactive protein (CRP) was observed in HTLV-1 positive patients than in HTLV-1 positive patients (P = 0.003). The value of disease activity score in 28 joints (DAS28) and the levels of erythrocyte sedimentation rate (ESR) tended to be higher in HTLV-1 positive patients. The discontinuation rate of anti-TNF was higher in HTLV-1 positive patients 6 months after the beginning of treatment than in HTLV-1 negative patients (30 % v.s 0 %, respectively). Most of reason for discontinuation was inefficacy of anti-TNF. EULAR response rate in 3 months of the treatment was worse in HTLV-1 positive patients than in HTLV-1 positive patients. The levels of CRP, ESR and the value of DAS28 remained to be significantly higher in carrier RA than non-carrier RA. There is no development of lymphoma or myelopathy during 2-years observation period in HTLV-1 positive patients. <h3>Conclusions</h3> The result of this small study suggested that HTLV-1 positive RA patients have high inflammation and resistance to the treatment with anti-TNF. Further study with larger number of cases is necessary to confirm these data. <h3>Disclosure of Interest</h3> None Declared
PROGNOSTIC SIGNIFICANCE OF INFARCT CORE PATHOLOGY IN ST-ELEVATION MYOCARDIAL INFARCTION SURVIVORS REVEALED BY QUANTITATIVE T2-WEIGHTED CARDIAC MAGNETIC RESONANCE
Authors: David Carrick, Caroline Haig, Sam Rauhalammi, Nadeem Ahmed, Ify Mordi, Margaret McEntegart, Mark Petrie, Hany Eteiba, Stuart Hood, Stuart Watkins, Mitchell Lindsay, Ahmed Mahrous, Aleksandra Radjenovic, Ian Ford, Niko Tzemos, Keith Oldroyd, Colin Berry
Journal: Journal of the American College of Cardiology (2015)
Aspirin Use in Patients with Major Upper Gastrointestinal Bleeding and Peptic-Ulcer Disease
Authors: Micha Levy
Journal: New England Journal of Medicine (1974)

Original Article from The New England Journal of Medicine — Aspirin Use in Patients with Major Upper Gastrointestinal Bleeding and Peptic-Ulcer Disease — A Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center
Abnormal Bile-Salt Patterns and Intestinal Bacterial Overgrowth Associated with Malabsorption
Authors: I. H. Rosenberg, W. G. Hardison, D. M. Bull
Journal: New England Journal of Medicine (1967)

IN a variety of diseases involving the intestine, malabsorption has been attributed to the proliferation of bacteria in the small intestine and therapy directed against the organisms has reversed the malabsorption.1 2 3 4 5 When the organisms have been isolated, they have been identified as normal colonie flora or, less commonly, normal mouth and throat bacteria.4 8 The mechanism by which these otherwise nonpathogenic organisms might produce steatorrhea has not been defined. Recent attempts to explain this phenomenon have focused attention on alterations in bile-salt metabolism in these patients.6 , 7 Normally, bile salts are excreted into the duodenum entirely in the conjugated form,9 in which . . .
Abstract 2625: Is familial risk of cancer limited to relatively early onset cases
Authors: Elham Kharazmi, Mahdi Fallah, Kristina Janquest, Kari Hemminki
Journal: Cancer Research (2012)

Abstract Purpose: It is widely believed that familial cancers are of early onset. We aimed to find out whether familial risk of cancer is limited to relatively early onset cases. Methods and material: Standardized incidence ratios (SIR) were calculated for familial risk in offspring by parental age at diagnosis in the nation-wide Swedish Family-Cancer Database including all Swedes born after 1931 with their biological parents, totaling &amp;gt;12.2 million individuals and including &amp;gt;1.1 million first primary cancer cases. Results: Median parental age at diagnosis in those whose offspring were affected with a concordant cancer was somewhat over 70 years. Some 56-86% of familial cancers in parents occurred at age over 69 years. Even when parents were diagnosed at advanced age (90+), the risk of concordant cancer in offspring was significantly increased for skin (SIR=2.1), colorectal (1.7), breast (1.6), and prostate cancer (1.5). In offspring aged 60 to 76 years whose parents were affected with a concordant cancer, almost none of the cases had a parent affected at &amp;lt;40 years. Conclusion: Despite the common believe that familial cancers are of early onset, the majority of familial cancers occur at advanced ages. Familial cancers may not be early onset in those whose probands were affected at advanced ages, which may suggest concordance of age of onset in familial cancers. We identified reliable familial risks for skin, colorectal, breast, and prostate cancer even when parents were diagnosed at age 90+. The present study provides novel information, important for clinical counseling, cancer genetics and screening guidance. 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 2625. doi:1538-7445.AM2012-2625
Abstract 3268: Histological and biological effects of substituted quinolines (gap junction enhancers) in a spontaneous mammary tumor model
Authors: Stephanie N. Shishido, Thu Annelise Nguyen, Adelaide Delahaye
Journal: Cancer Research (2012)

Abstract Effective use of antineoplastic drugs depends on the ability to balance the killing of tumor cells against the inherent toxicity to the host. Antineoplastic agents that act primarily on rapidly dividing and growing cells produce multiple side effects and are dose limiting. In recent years, there has been the development of biologic response modifiers aimed at enhancing innate anti-tumor defense mechanisms. Previous publications showed that substituted quinolines possess potent inhibitory activities against breast cancer cells through the enhancement of gap junction intercellular communication. These drugs decrease 71% of xenograft breast tumors in nude mice. The objective of this project is to evaluate the effect of substituted quinolines in a spontaneous mouse mammary tumor model (PyVT). PyVT mice were used at three different stages (pre, early and late) to characterize histological and biological changes in the treated animals compared to controls. Substituted quinolines cause a decrease of tumor growth rate by 112%, 77%, and 57% in the pre, early, and late stages of tumor development, respectively. Treatment during the pre and early stages of tumor formation also resulted in a decrease in the total number of tumors. Western blot analysis of the pre stage tumors show that the gap junction protein connexin 43 is more expressed in treated animals compared to control and the contrary for connexin 46. In the early and late stages, connexin 43 is expressed less in treated mice than controls, and vice versa for connexin 46. The expression of these connexins in control tissue suggests that this is due to an overall increase in connexin 43 and a decrease in connexin 46 during tumor development and metastasis. Histology of vital organs showed no significant alteration in treated animals compared to controls. These findings provide evidence that substituted quinolines cause a significant tumor reduction in a spontaneous mammary tumor model with no obvious adverse effects. 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 3268. doi:1538-7445.AM2012-3268
PTU-096 Cost Efficiency Of Faecal Calprotectin In Assessing New Referrals With Altered Bowel Habit
Authors: K Bundhoo, A Aravinthan, K Lithgo, T Price, M Johnson
Journal: Gut (2014)

<h3>Introduction</h3> Altered bowel habits (ABH) is one of the commonest reasons for referral to the gastroenterology clinic. The spectrum of organic and functional bowel symptoms provides a diagnostic dilemma. Functional bowel disorders are common, occurring in 15–20% of Western populations.<sup>1</sup> Therefore, it is important not to create an economic burden by over-investigation. Faecal calprotectin (FC) is a protein released from neutrophilic leucocytes into the intestinal lumen in response to mucosal inflammation. It is a well-validated, non-invasive test that can differentiate between organic and functional bowel disease with 93% sensitivity and 96% specificity.<sup>2</sup> These features make FC measurement a useful objective test in guiding further investigations. <h3>Methods</h3> Over a 2 year period, all FC data was collected in new patients referred to the outpatient clinic for further assessment of ABH and where a diagnostic dilemma existed. Results were recorded as normal (&lt;50 μg/g), borderline (50–100 μg/g) or positive (&gt;100 μg/g) and correlated with the use of further endoscopic or radiological assessment. Department of Health (DoH) tariffs were used to assess cost burden and potential savings. <h3>Results</h3> 275 FC measurements were performed in new referrals where there was a dilemma about diagnosis or need for further investigation. Colonoscopy was spared in 71% (196/275), including 139/164 normals, 16/22 borderline and 35/89 positives. Despite a normal FC result, 25 patients underwent endoscopic investigation after initial assessment. Of these, 16 procedures were normal, 4 had diverticular disease and 2 had low grade dysplastic polyps. Some patients underwent CT colonography with positive findings in 4/17 of the normal FC group (3 diverticular disease, 1 incidental gastric malignancy), 0/2 with borderline FC and 8/15 with positive FC measurement (5 diverticular disease, 1 suspected ileal ulcer, 2 cancers). If all 275 patients had undergone colonoscopy the cost for the Clinical Commissioning Group (CCG) would be £154275. Risk stratifying with FC assessment reduced this to £44319, saving £109956. <h3>Conclusion</h3> Faecal calprotectin assessment saved 71% of possible colonoscopies in those new patients assessed for ABH where there was a dilemma as to whether endoscopic investigation was necessary. This provided clinicians with the confidence to diagnose and manage functional bowel symptoms earlier. FC testing also saved our CCG £109956 of potentially unnecessary colonoscopy with the simultaneous advantage of reducing endoscopy waiting times. <h3>References</h3> Drossman <i>et al</i>. Irritable bowel syndrome. A technical review for practice guideline development. <i>Gastroenterology</i>1997;112:2120–2137 Van Rheenen <i>et al</i>. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. <i>BMJ </i>2010;341:c3369 <h3>Disclosure of Interest</h3> None Declared.
Measurement of Fractional Flow Reserve to Assess the Functional Severity of Coronary-Artery Stenoses
Authors: Nico H.J. Pijls, Bernard de Bruyne, Kathinka Peels, Pepijn H. van der Voort, Hans J.R.M. Bonnier, Jozef Bartunek, Jacques J. Koolen
Journal: New England Journal of Medicine (1996)

The clinical significance of coronary-artery stenoses of moderate severity can be difficult to determine. Myocardial fractional flow reserve (FFR) is a new index of the functional severity of coronary stenoses that is calculated from pressure measurements made during coronary arteriography. We compared this index with the results of noninvasive tests commonly used to detect myocardial ischemia, to determine the usefulness of the index.
Syphilitic Chancre of the Tongue
Authors: Konrad Staines, Philip Sloan
Journal: New England Journal of Medicine (2011)

A 41-year-old man presented with a 6-week history of a painful, nonhealing lesion on the dorsum of his tongue. Examination revealed an ulcer with a raised, indurated margin (Panel A). Malignancy and other infections were considered in the differential diagnosis. There was no lymphadenopathy on examination. A chronic inflammatory infiltrate with mature plasma cells and a granulomatous component was evident on incisional biopsy. Immunohistochemical staining for Treponema pallidum identified spirochetes in the granulation tissue overlying the ulcer, as well as in the walls and lumen of the capillaries at its margin (Panel B, arrows). A strongly positive treponemal antibody absorption . . .
Abstract 5359: Cytotoxicity of MLN8237 and SAHA in pediatric cancer cell lines
Authors: Jodi Muscal, Kathy Scorsone, Jeffrey Ecsedy, Stacey Berg
Journal: Cancer Research (2011)

Abstract Purpose: Children with recurrent or refractory tumors often have a poor prognosis. Innovative drug combinations are necessary to increase their disease-free and overall survival. Background: MLN8237 is a reversible inhibitor of the Aurora A serine/threonine kinase that showed excellent activity against several tumor types in the Pediatric Preclinical Testing Program. SAHA is a pan-histone deacetylase (HDAC) inhibitor that has shown pre-clinical activity in leukemia, lymphoma, neuroblastoma, and medulloblastoma. HDAC inhibitors decrease Aurora kinases by a variety of mechanisms, and HDAC inhibitors and Aurora kinase inhibitors disrupt the spindle assembly checkpoint at different points, suggesting that the combination could have increased antitumor activity. Methods: We investigated the combination of MLN8237 and SAHA in pediatric cancer cell lines, Molt-4 (pediatric T-cell ALL), IMR32 (neuroblastoma), and Daoy (medulloblastoma). Cell viability was measured using a modified methyl tetrazolium assay after 72 hours of drug treatment, and the cytotoxicity of the drug combination was analyzed using the universal response surface approach as implemented in ADAPT II modeling. For each single drug experiment, two replicate plates were tested, and for the combination drug experiments, four replicate plates were tested. Results: Our results showed that the single agent IC50 for MLN8237 is 0.02 – 0.04 μM in all cell lines. For SAHA, the single agent IC50 ranged from 0.5 μM for Molt-4 to 2.7 μM for Daoy. Both SAHA and MLN8237 inhibited cell survival in a concentration-dependent fashion. Treatment with SAHA resulted in nearly complete inhibition of cell growth in Molt-4 and IMR32 cells at concentrations &amp;gt; 1 μM and 80% inhibition of Daoy cell growth at the maximum concentration of 10 μM, which is well above the clinically relevant concentration range. Maximum inhibition of cell growth in all three lines occurred with 0.05-0.5 μM MLN8237. At concentrations of MLN8237 exceeding approximately 1 μM, there was a paradoxical increase in viability signal in all three lines, most pronounced for Daoy. This may be explained by inhibition of Aurora B kinase which occurs at higher MLN8237 concentrations. Aurora B inhibition leads to metabolically active multinucleated cells. The combination of MLN8237 plus SAHA showed additive cytotoxicity in all three cell lines and nearly abrogated the survival noted at high single-agent MLN8237 concentrations. Conclusion: These results provide important preclinical support for the development of future clinical studies of MLN8237and SAHA. 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 5359. doi:10.1158/1538-7445.AM2011-5359
The Response of Breast Cancer Initiating Cells to Fractionated Radiation.
Authors: C. Lagadec, E. Vlashi, L. Della Donna, F. Pajonk
Journal: Cancer Research (2009)

Abstract Recent experimental data provide evidence for a hierarchical structure of many solid cancers including breast cancer. Using surface markers, a small population of highly tumorigenic breast cancer initiating cells (CICs) has been prospectively identified, which exhibited a cancer stem cell phenotype, thus being able to self-renew and to give rise progeny of multiple different lineages of differentiated cells. We previously demonstrated that this population of cells was relatively resistant against ionizing radiation if compared to their non-tumorigenic counterparts. Furthermore, we reported that this population of CICs increased during the course of fractionated irradiation. The extent of the remaining self-renewing capacity and multi-lineage potency of these CICs after fractions of radiation is currently unknown. However, this information is crucial for evaluating the significance of radiation resistance of CICs.In the present study, we hypothesized that CICs not only survive fractions of ionizing more likely than their non-tumorigenic counterparts but also retain the CSC phenotype as defined by operational means and may even become more aggressive than populations of non-irradiated control CICs.Using CD24, CD44, ESA, and lack of proteasome function to identify breast cancer CICs we investigated their response to fractionated radiation and showed that CICs cells are more resistant to radiation (from 2Gy to 8x2Gy) than non-tumorigenic cells. At 2Gy, the stem cells population CD44high/CD24-/low in monolayer increased 3 times (from 0.25% at 0Gy to 0.74% at 2Gy). The analysis of CICs population after 8x2Gy demonstrated than the CICs containing population was not affected at higher total doses (0.25% at 0Gy and 0.28% at 8x2Gy). A sphere forming capacity assay demonstrated self-renewal capacity of the survivig CICs after irradiation (2Gy: +93% or 8x2Gy: +105%).Using low proteasome to identify stem cells and membrane labeling (PKH26) we analyzed the effect of fractionated irradiation treatment (0, 3Gy, 2x3Gy, 3x3Gy 4x3Gy and 5x3Gy) on CIC and non-tumorigenic cell proliferation. We demonstrated that CSCs irradiated with 3Gy or 2x3Gy lost the PHK26 dye faster than the control indicating recruitment of these cells into the pool of cycling cells (mean division of CSCs; 0Gy: 2.6, 3Gy or 2x3Gy: 3), while an treatment with 5x3Gy still enriched for CSCs but the reduction of proliferation rate of CSCs indicated that this enrichment is essentially due to their radioresistant phenotype (mean division; 5x3Gy: 1.9). Tumorigenicity of double positive and double negative cell was tested in limiting dilution assay using a mouse model (Rag2-/-IL2Rγc-/-).We conclude that radiation resistant CICs not only survive fractionated radiation but retain their CSC phenotype. This indicates that radiosensitizing CICs could be a reasonable approach to improve treatment outcome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1153.
Abstract 869: Potent <i>in vitro</i> and <i>in vivo</i> anti-tumor activity of PI3K inhibitor BAY 80-6946 and MEK inhibitor BAY 86-9766 in preclinical biliary tract cancer models
Authors: Andrea Haegebarth, Katja Haike, Katja Haike, Juliane Paul, Dominik Mumberg, Karl Ziegelbauer, Ningshu Liu
Journal: Cancer Research (2012)

Abstract Biliary tract cancer (BTC) includes a spectrum of genetically diverse invasive adenocarcinomas consisting intra- and extrahepatic cholangiocarcinoma (CC), and carcinoma arising from the gall bladder (GBC). Only 10% of patients diagnosed with early-stage disease are considered candidates for surgical resection, which offers the only chance for cure. The prognosis is poor for the majority of patients with locally advanced or metastatic BTC with a median survival of under a year. Recently, high incidence of oncogenic mutations such as KRAS, BRAF, PIK3CA and EGFR were found in BTC patients, potentially rendering these patients sensitive to inhibitors of these pathways. We report on preclinical evaluation of highly potent and selective PI3K inhibitor BAY 80-6946 and allosteric MEK inhibitor BAY 86-9766 in BTC as single agent and in combination. In vitro profiling a panel of BTC tumor cell lines indicated that KRASmut and PIK3CAmut cell lines were sensitive to MEKi (BAY 86-9766) and PI3Ki (BAY 80-6946), respectively, compared to the cell lines with wild type KRAS and PIK3CA. However, although MEKi BAY 86-9766 inhibited proliferation with IC50s of 147 nM in HuCCT-1 (KRASG12D) and 137 nM in EGI-1 (KRASG12D) cell lines, it can neither reach IC90 nor induce tumor apoptosis at concentration up to10 µM, indicating activation of additional survival pathways in these KRASmut BTC cell lines. When combining MEKi BAY 86-9766 with PI3Ki BAY 80-6946 in KRASmut EGI-1, IC90 could be reached at much lower concentrations, e.g. 108 nM of MEKi with 81 nM of PI3Ki in EGI-1 cells. Furthermore, strong activation (10-fold) of caspase3/7 was observed when EGI-1 cells were treated with 700 nM of MEKi with 230 nM of PI3Ki. To confirm the observed in vitro synergies, anti-tumor efficacy of BAY 80-6946 and BAY 86-9766 in mono- as well as combination therapy was evaluated in a set of human BTC xenograft models. Similar to the in vitro results, robust in vivo antitumor activities were observed in the PI3Ki and MEKi combination groups compared to monotherapy arms. Further detailed molecular mechanism on the synergistic inhibition of BTC tumor growth by combination of PI3K and MEK inhibitors, as well as in vitro and in vivo comparison to the chemotherapeutics will be presented. In conclusion, PI3Ki and MEKi combination therapy might open a new treatment paradigm for BTC to be developed in clinic. 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 869. doi:1538-7445.AM2012-869