tbuckley/cabot-search huggingface dataset:
Abstract BSF1-1: Single Cell Analysis of Normal and Tumor Breast Epithelium Reveals Differential Use of Signalling Pathways by Novel Populations
Authors: MF Clarke, Lobo N
Journal: Cancer Research (2010)

Abstract Primary human tissue contains a complex mixture of cell types which can only be partially purified by cell sorting based on surface markers. To gain further insight into mammary gland and tumor biology, we performed highly parallel single cell multiplexed gene expression measurements on individual normal and malignant mammary cells. This approach enabled discovery of novel normal mammary stem cell markers and gave insights into normal and malignant tissue architecture. We identified two distinct normal mammary stem cell populations: a proliferating, stem cell population that expresses basal cell markers and shows evidence of activation of the Wnt/β-catenin signaling pathway components and a second, Axin2-, CD44-/low quiescent normal stem cell population which does not express basal cell markers. Both populations had similar engraftment ability in vivo, demonstrating that there are likely two physiological stem cell states. Single cell analysis of estrogen receptor positive (ER+) breast tumors revealed similar cellular populations in cancer cells that resemble the normal mammary duct architecture. Remarkably, the expression of therapeutic targets such as growth factor receptors and the estrogen receptor differed between the different cell compartments. Most notably, the Axin2- cell population did not express ER or TOPO2, the target of Adriamycin, one of the most effective drugs for the treatment of breast cancer, suggesting that this population is not directly targeted by many therapeutic agents routinely used for the treatment of ER+ breast cancer. Our results show that single cell analyses might be useful for developing new strategies for treating cancer by identifying the expression of therapeutic targets by each of the cancer cell populations that make up a particular tumor. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr BSF1-1.
ASSOCIATION OF GENOTYPING WITH PLATELET ACTIVATION AND CARDIOVASCULAR OUTCOME IN PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION RECEIVING CLOPIDOGREL: TWO PIECES OF THE PUZZLE OF CLOPIDOGREL RESISTANCE
Authors: Gerasimos Siasos, Stamatios Kioufis, Evangelos Oikonomou, Marina Zaromitidou, Manolis Vavuranakis, Konstantinos Maniatis, Eleni Kokkou, Nikolaos Gouliopoulos, Konstantinos Mourouzis, Sotirios Tsalamandris, Athanasios Papavassiliou, Christodoulos I Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Abstract 5558: Lurbinectedin (PM01183) specifically targets RNA Pol II for degradation via the proteasome pathway in a TC-NER-dependent fashion.
Authors: Gema Santamaria, Juan F. Martinez-Leal, Carmen Cuevas, Luis F. Garcia-Fernandez, Carlos M. Galmarini
Journal: Cancer Research (2013)

Abstract Lurbinectedin (PM01183), a new synthetic tetrahydroisoquinoline alkaloid, is a minor groove specific DNA binder that interacts directly with specific factors involved in DNA repair and transcription pathways. In living cells, PM01183-DNA adducts stall replication and transcription giving rise to double strand breaks, inducing accumulation of cells in the S-phase of the cell cycle and triggering apoptosis. In both the ongoing phase II trials (pancreas and platinum-resistant ovarian cancer) the first stage was concluded with positive results in clinical activity, ensuring the continuity of the studies. Also, phase I trials in combination with doxorubicin and gemcitabine as well as in advanced acute leukemia are ongoing. Here, we examined the effects of PM01183 on the activity and stability of the RNAPol II as well as on other factors of the transcriptional machinery, including TBP (TFIID), p62 (TFIIH), XPG and XPF. Our results showed that PM01183 induced a rapid, time- and concentration-dependent degradation of RNA Pol II in a panel of different human tumor cell lines, including HCT-116 (colon), A549 (NSCLC), HeLa (cervix) and A763 (sarcoma). This degradative process was efficiently abrogated in the presence of transcriptional (DRB or Actinomycin D) or proteasome inhibitors (MG132), demonstrating that PM01183 specifically targets the transcriptionally active RNA Pol II for degradation via the proteasome pathway. In addition, it was also shown that the effect of PM01183 on the RNA Pol II was dependent on the presence of a functional TC NER repair machinery. PM01183 induced degradation of RNA Pol II in global NER (XPC) deficient cells, but failed to do it in TC NER (CSB, XPD and XPG) deficient cells. Importantly, these effects were confirmed to be specific for the RNA Pol II, since other factors of the transcriptional machinery, such as TBP (TFIID), p62 (TFIIH), XPG or XPF or the RPA194 subunit of the RNA Pol I were not affected. Together, these results show up the complex mechanism of action of the drug on tumor cells. Citation Format: Gema Santamaria, Juan F. Martinez-Leal, Carmen Cuevas, Luis F. Garcia-Fernandez, Carlos M. Galmarini. Lurbinectedin (PM01183) specifically targets RNA Pol II for degradation via the proteasome pathway in a TC-NER-dependent fashion. [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 5558. doi:10.1158/1538-7445.AM2013-5558
Danish contributions to the evaluation of serum therapy for diphtheria in the 1890s
Authors: Christian Gluud
Journal: Journal of the Royal Society of Medicine (2011)

Diphtheria's effects are caused by a toxin produced by the bacterium Corynebacterium diphtheriae. This toxin produces not only diphtheria's effects in the upper respiratory tract, but also later complications, including myocarditis and peripheral neuropathy. These complications, and superinfection with other bacterial pathogens (streptococci, in particular), contribute to the serious morbidity and mortality associated with the disease.

In the early 1890s, in Berlin, Emil von Behring and Shibasabura Kitasato developed a serum from a hyper-immune horse, which seemed to confer passive immunity on patients with diphtheria. Experience with this serum was first reported in a paper published in 1893.1 The following year, Emile Roux, Louis Martin and Auguste Chaillou reported detailed information on 448 children admitted to the diphtheria service of the Hopital des Enfants-Malades in Paris. One hundred and nine of the 448 children admitted died – a fatality of 24.5%. This compared very favourably not only with a rate of about 50% in the same hospital during the four years 1891 to 1893, but also with a fatality of 60% in the Hopital Trousseau, where serum had not been used.2,3

The evidence from Paris and other evidence using historical controls did not convince everyone of the value of anti-diphtheritic serum, however. The debate was complicated both because the disease was undergoing spontaneous fluctuations with decreasing virulence and by claims that the success of serum treatment showed that laboratory research was a more promising approach to tackling diseases associated with poverty than the social reforms for which Virchow and others had been calling.4 Furthermore, deaths had been attributed to the antitoxin, some of which attracted wide publicity.4–6
AB0013 First report of erbb3 gene association with rheumatoid arthritis predisposition
Authors: A. Chatzikyriakidou, P. V. Voulgari, A. A. Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Genome wide association studies revealed that type 1 diabetes (T1D) and rheumatoid arthritis (RA) share many genetic loci. Recently, ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3) gene was reported to be related strongly with T1D predisposition. Furthermore, ERBB3 was reported i) to be expressed on the surface of CD11c+ cells (monocytes and dendritic cells), ii) to correlate with the ability of APC to stimulate T cell proliferation, and iii) to play critical role in the activation of the ERBB3-PI3K-Akt cascade while disturbances in its activation have been associated with reduced numbers of regulatory T cells. The aim of the present study was to search ERBB3 gene association with RA liability. <h3>Methods</h3> One hundred and eighty-six RA patients and 147 controls were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism assay was conducted in rs2271189 and rs2292239 genotyping. <h3>Results</h3> Statistical significant difference was observed in rs2271189 alleles' distribution between RA patients and controls (p = 0.029, OR: 1.460, 95% CI: 1.040-2.050). <h3>Conclusions</h3> As far to our knowledge, this is the first study which correlates ERBB3 gene with RA susceptibility adding to a previous report of chromosome 12q13 association with RA liability. Furthermore, we confirmed that polymorphism rs2271189 can predict better ERBB3 gene association with disorders than the previously reported ERBB3 variants. In conclusion, more studies are needed in larger groups of patients in order to increase the power of the observed here genetic association, while functional studies of ERRB3 gene could specify its mode of function in immune related diseases. <h3>Disclosure of Interest</h3> None Declared
OP0170 The Radiocarpal and MCP2 Joints Should be Included in Ultrasonographic Follow-Up of RA Patients During Biologic Treatment
Authors: H. B. Hammer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasound (US) (grey scale (GS) and power Doppler (PD)) is sensitive for scoring of synovitis in patients with rheumatoid arthritis (RA), with excellent reliability for semi-quantitative scoring (0-3) of GS and PD with an US atlas as reference. Thus it may be used for follow-up of patients with RA during biologic treatment. So far there is no consensus on the number of joints to be included. <h3>Objectives</h3> To assess which are the most often involved joints in patients with established RA and the response of the different joints to biologic medication. <h3>Methods</h3> 172 RA patients (aged mean (SD) 58 (12) years, disease duration 7 (5) years, 78% women, 82% anti-CCP positive) consecutively included when starting biologic treatment (infliximab (n=27); etanercept (n=54); adalimumab (n=20); certolizumab (n=10); golimumab (n=10); rituximab (n=29); tocilizumab (n=13); abatacept (n=9)) were examined by US (with the US atlas as reference) of 36 joints (wrist (radiocarpal, intercarpal, radioulnar), MCP 1-5, PIP 2 and 3, elbow, knee, talocrural, MTP 1-5). 81 patients were re-examined after 12 months. GS score ≥ 2 and PD score ≥ 1 were defined as inflamed joints. The mean percentage (of right/left involvement) for each joint was calculated. <h3>Results</h3> At baseline the individual joints had GS score ≥ 2 in 12-41% and PD score ≥ 1 in 7-53% of patients. There was significantly reduced prevalence at 12 months follow-up for all joints (table). The median (range) differences in involvement of right vs left side of the individual joints were at baseline/follow-up 2(0-7)/ 5(0-9)% for GS and 3(0-7)/ 3(0-7)%, for PD. At baseline the radiocarpal and MCP 2 joints were most often involved (both GS synovitis and PD activity in ≥40% of patients). <h3>Conclusions</h3> Bilateral examination of radiocarpal and MCP2 joints should be included in US assessments of RA patients. However, except for low prevalence of arthritis in knee and ankle joints, all the examined joints were frequently involved and could be candidates for US scoring. Thus, a comprehensive US assessment may be necessary to ensure a high sensitivity for detecting inflammation in follow-up of RA patients on biologic medication. <h3>Disclosure of Interest</h3> None Declared
CLINICAL PREDICTORS RELATED TO DELAYED DIAGNOSIS OF ACUTE AORTIC DISSECTION IN THE EMERGENCY ROOM
Authors: Kazuhito Hirata, Minoru Wake, Takanori Takahashi, Jun Nakazato, Nobuhito Yagi, Tadayoshi Miyagi, Junichi Shimotakahara, Tsuyoshi Takara, Toshiho Tengan
Journal: Journal of the American College of Cardiology (2015)
AB0235 Low vaccination status of patients with ra treated by biological drugs and dmards in czech republic
Authors: K. Pavelka, E. Moster, H. Ptackova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The risk of infections is increased by patients with RA. There is increasing evidence, that biological agents can contribute to risk of both non serious and serious infections. Vaccination is attractive method to prevent certain infections. Numerous studies have documented good efficacy of vaccinations treated by biologic drugs. ACR and EULAR have developed recommendations for vaccination of adult patients with rheumatic diseases (1). Nevertheless, how it is reflected in clinical practise is not known. <h3>Objectives</h3> To evaluate, how the patients with rheumatic inflammatory diseases treated by DMARDS and biologics are vaccinated in Czech Republic. <h3>Methods</h3> Crossectional study using special questionnaire. Study was performed in one academic tertiary centrum and two country private practices not using biologic therapy. Research was performed in second half of 2013. <h3>Results</h3> 340 patients have been included in study. The diagnosis was RA (220) 65 %, ankylosing spondylitis (77) 22,7 %, psoriatic arthritis (39) 11,5 % and SLE (3) 0,9 %. The mean age was 51,3 ± 14,4 years, duration of disease 13 years and male to female 33,6 % vs. 66,4 %. The proportion of patients in academic centrum to private practises was 231 (108) 68 % vs. 32 %, 31 % of patients were on DMARDs only, 69 % on biologics (ADA 28 %, INF 8 %, GOL 13 %, REM 8 %, ETA 3 %, RIT 4 %, ABA 2 %). Before initiation of immunosuppressive therapy 57 % were vaccinated for tetanus,18,8 % for flue, 9,4 % for hepatitis B, 6,5 % for hepatitis B, 2,9 % for pneunoccoc, 0,9 % for Hemophilus infl. and 0,6 % for Neisseria meningitis. During biologic / DMARD therapy were treated 35 % of patients. The vaccination status has been assessed in initial work–up in 42 % of patients. It was actively offered to 28,5 % of patients only 33 % of patients would have agreed on offer of vaccination and 66 % not. Approximately 50 % of patients agreed of payment for preventive vaccination before biologic therapy. <h3>Conclusions</h3> Despite EULAR and Czech Rheum Soc. recommendations vaccination status is very low and only 18 % of patients is vaccinated for flue and 3 % for pneumoccocus. Based on these results, we suggest education campaign for both doctors / patients. We also initiate discussion with authorities for better reimbursement of vaccination for patients with inflammatory rheumatic diseases treated by biologic drugs. <h3>References</h3> Refeences: van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2011;3:414-422 <h3>Acknowledgements</h3> Key words: vaccination, rheumatic diseases, biologic therapy. Supported by grant of Ministry of Health Czech Republic Nr. NT12437 <h3>Disclosure of Interest</h3> K. Pavelka Grant/research support from: Ministry of Health Czech Republic Nr. NT12437, E. Moster: None Declared, H. Ptackova: None Declared
Scrotal Peritoneal Mesothelioma on PET/CT
Authors: Salih Ozguven, Mustafa Aras, Fuat Dede, Tunc Ones, Halil Turgut Turoglu
Journal: Clinical Nuclear Medicine (2014)

Although malignant mesothelioma originating from the tunica vaginalis has been reported in the literature, direct invasion of malignant peritoneal mesothelioma to the scrotal cavity has not been described yet. Herein, we presented a diffuse malignant peritoneal mesothelioma extending inferiorly to the scrotum via inguinal canal detected on FDG PET/CT.
PTH-078 Forward Progress Or Financial Extravagance? Counting The Cost Of Nice Guidelines For Chronic Hepatitis B
Authors: B Hudson, H Badham, TY Lim, H Morrison, CA McCune, AJ Portal, PL Collins, FH Gordon
Journal: Gut (2014)

<h3>Introduction</h3> An estimated 180,000 people in the UK are chronically infected with hepatitis B (HBV). NICE guidelines published in 2013 advocate changes in the management of this patient group. Recommendation toward use of peginterferon alfa-2a (PEG-IFN) as first line therapy, a reduced threshold for treatment initiation, and the monitoring of chronically infected individuals with annual elastography hold particular resource implications. University Hospitals Bristol (UHB) serves a largely urban population of approximately 350,000, encompassing large immigrant communities, including a Somali population of approximately 10,000. UHB provides an elastography service to an additional 3 district hospitals. Through analysis of our existing HBV patient population the resource implications of adopting 2013 NICE guidelines, in contrast to 2012 EASL guidelines, are assessed. <h3>Methods</h3> Local HBV databases were scrutinised to identify all HBV patients attending over a one year period from november 2012. Patients defaulting follow-up during this period were excluded. A cost of treatment analysis was undertaken by reassessing each patient’s treatment eligibility according to 2013 NICE guidance. Additional monitoring and clinic follow up costs were also calculated. <h3>Results</h3> 154 patients were identified, 93 of whom were receiving antiviral nucleos (t)ide analogue treatment (24 initiated). 2 had initiated PEG-IFN. 61 were under monitoring only. All 24 patients starting therapy met NICE criteria for PEG-IFN, the excess cost of which was £137,003 over a 1 year period. The estimated additional number of treatment clinic visits for this group is 202 (assuming an extra 8.4 visits/patient initiated). This analysis does not include increased demand for liason psychiatry and virology services. There would be 109 extra elastography appointments required for this cohort alone, amounting to a further 28 clinics a year. 3 district general hospitals currently refer patients to UHB for elastography, and this analysis does not account for the inevitable increase in such referrals. <h3>Conclusion</h3> Implementation of 2013 NICE guidelines for management of chronic HBV represent a significant challenge to NHS resources. In addition to increased drug expenditure, markedly increased clinic capacity and specialist nurse provision will be required in our centre to facilitate increased used of PEG-IFN and to provide sufficient transient elastography for our region. Additional demands on virology and liason psychiatry services are also likely. Practical suggestions for improving efficiency and capacity, such as ‘one stop’ fibroscan and follow up clinics, are discussed. <h3>Disclosure of Interest</h3> None Declared.
Endovascular Stents for Iliac Arterial Disease
Authors: K Rosenfield, J M Isner
Journal: New England Journal of Medicine (1993)

Figure 1. Endovascular Stents for Iliac Arterial Disease. The angiogram shown in Panel A was recorded in a 57-year-old man with no right femoral pulse; arrows indicate a 5-cm total occlusion of the right common iliac artery. The occlusion was crossed with a hydrophilic guidewire. An angiogram recorded after angioplasty (Panel B) shows a patent common iliac artery with extensive dissection. A final angiogram (Panel C) was recorded after the tandem insertion of two endovascular stents and shows that the artery is widely patent. The non-expanded iliac stent (Johnson and Johnson, Piscataway, N.J.) is shown in Panel D, and the . . .
Inclusion and exclusion criteria in phase III trials with systemic agents in psoriasis: the external validity of drug development
Authors: N. Kirsten, C. Bulai Livideanu, M.A. Richard, M.P. Konstantinou, A. Khemis, C. Balluteaud, C. Goujon, M. Beylot-Barry, C. Paul
Journal: British Journal of Dermatology (2016)
Environmental Tobacco Smoke in Passenger Cabins of Commercial Aircraft
Authors: G. B. OLDAKER
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Environmental Tobacco Smoke in Passenger Cabins of Commercial Aircraft Get access GUY B. OLDAKER GUY B. OLDAKER R. J. Reynolds Tobacco Company Bowman Gray Technical CenterWinston-Salem, NC 27102 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 18, 20 September 1989, Pages 1424–1425, https://doi.org/10.1093/jnci/81.18.1424 Published: 20 September 1989
Long-term follow-up results of endoscopy-assisted breast surgery (EBS) for early breast cancer.
Authors: C Yom, H Min, Y Park, W Bae
Journal: Cancer Research (2009)

Abstract Abstract #4145 Introduction: Although endoscopy-assisted breast surgery(EBS) for early breast cancer had shown the excellent cosmetic outcomes, the application of ESSB is still controversial because of the scanty evidence of long-term safety and feasibility. This study is to evaluate the long-term outcome of endoscopy-assdisted breast surgery compared to conventional breast surgery for early breast cancer.&amp;#x2028; Patients and Methods: Between January 2002 through December 2006, 76 patients(Group E) who had diagnosed breast cancer underwent EBS at Sungkyunkwan University Kangbuk Samsung Hospital. 52 patients(Group O) not greater than stage 2A who had undergone conventional breast surgery during same period were enrolled in this study. The clinicopathologic characteristics, postoperative outcomes, hospital courses, and long-term outcomes including cancer recurrence and 5 year survival were retrospectively compared between two groups. The survivals of all the patients were confirmed with 58.4 month median follow up duration. Results: Tumor sizes were larger in Group O than in Group E(p=0.000). Harvested lymph nodes were more in Group O than in Group E(p=0.000). Postoperative recovery was significantly faster in the Group E; drain was removed earlier(p=0.001) and the postoperative hospital stay was shorter(p=0.001). The mean operation time was significantly longer in the Group E(p=0.000). There were no differences in the operation related morbidity and mortality between the two groups. In comparison of adjuvant therapy, Group O were received more chemotherapy than Group E(p=0.018), but there were no statistical differences of radiotherapy and hormonal therapy between two groups. Subjective cosmetic results were excellent in 63.6% and good in 18.2% more than 1 year after surgery. There was follow-up loss in 3 cases. Cancer-related death occurred in only 1 patient(0.7%) in Group O. The overall 5-year survival rate(5YSR) of the Group O and Group E were 98.2% and 100% , repectively. The disease-free 5YSR of Group O and Group E was 91.3% and 86.9%, repectively. There were no statistical differences on the overall and disease-free 5YSR between the two groups(p=0.446, p=0.205). Cancer recurrence occurred in 5 cases including 2 local recurrences, 2 distant metastases, and 1 second non-breast primary cancer in Group O and 6 cases including 2 local recurrences, 2 regional recurrences, 1 distant metastasis and 1 second non-breast primary cancer in Group E and there was no statistical significance between two groups(p=0.787).&amp;#x2028; Conclusions: Although the number and the qualification of the patients were so limited, our data suggest that endoscopy-assisted skin sparing breast surgery for early breast cancer is feasible and safe comparing to conventional breast surgery. We expect the results of the present study to be confirmed by prospective randomized analysis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4145.