tbuckley/cabot-search huggingface dataset:
PWE-099 Direct Detection Of Thiopurine Metabolites In Erythrocytes And Leukocytes Using A Novel Lcms/ms Method To Interrogate Drug Response And<i>in Vivo</i>Metabolism: Abstract PWE-099 Table 1
Authors: SA Coulthard, P Berry, S McGarrity, CP Redfern, A Ansari
Journal: Gut (2014)

<h3>Introduction</h3> One of the major issues hampering the understanding of metabolism and response to thiopurine drugs (azathioprine (Aza), mercaptopurine (MP) and thioguanine (TG)) is the indirect method for measuring their metabolites in red blood cells (RBC) after pre-analytical processing. RBC which lack inosine-monophosphate dehydrogenase, critical for bioconversion of thiopurines, do not reflect thiopurine metabolism in peripheral mononuclear cells (PMC)) as exemplified by the poor concordance between metabolite levels and clinical response. To address this problem we have developed a ‘direct method’ of measuring thiopurine metabolites in both RBC and PMC. <h3>Methods</h3> PMCs and RBCs were isolated from blood samples of thiopurine (low dose aza/allopurinol (LDAA), TG or MP) treated patients. They were separated by Lymphoprep, sonicated, centrifuged and 50 uL of supernatant injected for chromatographical separation of the metabolites and analysed on a API4000 triple quadrupole LC-MS/MS. Standard curves and controls validated and metabolite levels reported as pM of metabolites/mg of protein. <h3>Results</h3> Concentrations of metabolites in both RBC and PMCs were determined from standard curves (7.8 -500 nM) and expressed relative to protein concentration. Comparison between these and results from commercially available RBC metabolite levels are shown below. Sum of methylated metabolites from the LCMS/MS includes methylated thioguanine nucleotides. Undetected metabolites listed as ND <h3>Conclusion</h3> The metabolite profiles between patients on FDA, LDAA and TG are very different indicating that these treatments have distinct metabolic pathways. The direct and commercial methods are also different in metabolic profiles raising the suspicion that the commercial method is not an accurate reflection of true metabolic profiles in RBCs. The clinical implication from these data is that the choice of drug protocol (LDAA in “high methylators”) is not based on reliable methods. To confirm this, these data and other markers of response and efficacy are being collected prospectively to facilitate a more informed and deeper understanding of how and why FDA, LDAA and TG treated patients respond to these different drug protocols, with an ultimate goal of individualisation of therapy and improvement of the use of these cheap and established drugs. <h3>Disclosure of Interest</h3> None Declared.
MPs accuse Serco's out of hours GP service of a culture that led to cheating and dishonesty
Authors: A. O'Dowd
Journal: BMJ (2013)

The culture at a privately run, out of hours GP service in Cornwall was one that seemed to encourage staff to “cheat” and to feel uncomfortable with telling the truth, MPs have claimed.

Managers of Serco appeared before the House of Commons Public Accounts Committee on 22 April as part of the committee’s inquiry into out of hours GP services in Cornwall, which are provided by the company for NHS Kernow, the clinical commissioning group for Cornwall and Isles of Scilly.

Serco has been the subject of various reports critical of its service from the NHS regulator the Care Quality Commission and the National Audit Office.1 2 3 These were initially prompted by claims by several whistleblowers that the service was understaffed and was altering data to ensure that …
Abstract P4-06-21: Matrix Metalloproteinase 2 in Tumor Cell-Induced Platelet Aggregation: Regulation by Cryptotanshinone
Authors: Y Linggeng, L Yin, H Chenhu, R Junshan, Z Lei, T. Li
Journal: Cancer Research (2010)

Abstract Background: A correlation exists between the ability of tumor cells to aggregate platelets and their tendency to metastasize. Tumor cell-induced platelet aggregation (TCIPA) facilitates the embolization of the vasculature with tumor cells and the formation of metastatic foci. It is well documentedthat matrix metalloproteinases (MMPs) play an integral part in tumor spread and the metastatic cascade. Material and Methods: Therefore, we have examined the role of MMPs during TCIPA and its regulation by Cryptotanshinone in vitro. Human breast cancer cell line MCF-7 and MDA-MB-231 induced TCIPA in a concentration dependent manner that was monitored by aggregometry. This aggregation resulted in the release of MMP-2 from platelets and cancer cells, as measured by RT-PCR. Results:MCF-7 cells released significantly more MMP-2 than MDA-MB-231 cells and were more efficacious in inducing TCIPA. Inhibition of MMP-2 with phenanthroline (1-1000 mM), a synthetic inhibitor of MMPs, and by neutralizing anti-MMP-2 antibody (10 mg/ml) reduced TCIPA induced by MCF-7 cells. TCIPA was abolished by simultaneous inhibition of platelet function with acetylsalicylic acid (100 mM; thromboxane pathway inhibitor), apyrase (250 mg/ml; ADP pathway inhibitor), and phenanthroline. Cryptotanshinone inhibited TCIPA and MMP-2 release from platelets and tumor cells. Discussion:We conclude that (a) human Human breast cancer cells aggregate platelets via mechanism (s) that are mediated, in part, by MMP-2; (b) Cryptotanshinone inhibits TCIPA, in part, by attenuating the release of MMP-2. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-21.
780 UPREGULATION OF THE FAS-MEDIATED APOPTOSIS PATHWAY BY PERIPHERAL T CELLS IN HCV MONO-INFECTED AND HIV/HCV CO-INFECTED PATIENTS
Authors: M. Feuth, K.J. Van Erpecum, P.D. Siersema, A.I. Hoepelman, D. Van Baarle, J.E. Arends
Journal: Journal of Hepatology (2012)
Intertemporal bargaining predicts moral behavior, even in anonymous, one-shot economic games
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2013)

Abstract To the extent that acting fairly is in an individual's long-term interest, short-term impulses to cheat present a self-control problem. The only effective solution is to interpret the problem as a variant of repeated prisoner's dilemma, with each choice as a test case predicting future choices. Moral choice appears to be the product of a contract because it comes from self-enforcing intertemporal cooperation.
Valacyclovir for the Prevention of Cytomegalovirus Disease after Renal Transplantation
Authors: David Lowance, Hans-H. Neumayer, Christophe M. Legendre, Jean-Paul Squifflet, Josef Kovarik, Patrick J. Brennan, Douglas Norman, Rafael Mendez, Michael R. Keating, Gary L. Coggon, Adam Crisp, Ira C. Lee
Journal: New England Journal of Medicine (1999)

Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease.
PTH-165 Validating the Colonoscopy Waiting List - Challenging but Rewarding: Abstract PTH-165 Table 1
Authors: R Prudham, A Boyer
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopy services within the UK are under pressure with increasing demand predicted and a need to maintain timeliness. The Department of Health for England and Wales wishes to improve outcomes for colorectal cancer and so increase the volume of lower GI endoscopy. Endoscopy services must increase efficiency to meet this challenge. We felt there was an opportunity to increase quality and reduce variation by ensuring all scheduled colonoscopies complied with National and departmental guidance. This is a key quality standard of the Global Rating Scale. We identified sessions in job plans of 3 nurse endoscopists within our trust. We then identified the guidance, informed endoscopists and the management team of the exercise we were undertaking and finally evaluated the intervention to be shared within our directorate team. <h3>Methods</h3> Patients awaiting scheduled colonoscopy were identified form the Primary Targetted List database held by the trust to manage waiting and scheduled patients. Patients being followed up for colorectal cancer were excluded from the process and study as there was no single protocol being followed at the time of the study. The patient groups studied were therefore those on surveillance pathways for polyp follow up, family history or inflammatory bowel disease. Clinical teams within the trust were informed by the clinical director of the process and that BSG guidelines for the conditions listed above were to be followed. The initial phase of the process was undertaken by a single Nurse Endoscopist. Following validation against guidelines, the case was reviewed by the clinical director and a letter addressed to the patient and copied to the patient’s GP and secondary care consultant. The letter was co-signed by the nurse and the clinical director. Following the establishment of the process as feasible, two other nurse endoscopists were trained in validating the procedures. Sessions were identified in job plans to ensure this process could be perpetuated long term. <h3>Results</h3> Large numbers of surveillance colonoscopies are undertaken (73–124 per month). Many were listed on basis of colonoscopy findings and not checked for histology. A wide range of clinicians including non-endoscopists were listing patients. Guidelines were not adhered too. There was resistance to this standardisation from clinicians, GPs and patients initially. <h3>Conclusion</h3> Wide variations in practise were observed. A large number of unnecessary colonoscopies were deferred to a more appropriate interval, producing benefits in quality and efficiency using existing resources. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> BSG (2010) Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups BSG (2002) Surveillance following Adenoma Removal
Abstract 1836: Long noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free interval in human non-small cell lung cancer.
Authors: Takayuki Nakagawa
Journal: Cancer Research (2013)

Abstract Lung cancer is the most common cause of cancer death worldwide. Non- small cell lung cancer (NSCLC) occupies more than 80% of all lung cancer. Overall, less than 10% of patients diagnosed with NSCLC survive five years after the diagnosis. Multidisciplinary management of NSCLC which contains surgery, chemotherapy and radiotherapy does not satisfactorily improve the patients’ prognosis. The pathogenic mechanisms contributing to the resistance to various therapeutic approaches in this cancer still remain to be clarified. HOTAIR is one of the large intervening noncoding RNA and interacts with the polycomb repressive complex 2 (PRC2) in the regulation of gene activities. Recently, the enhanced expression of this molecule has been shown to be associated with metastasis and/or poor prognosis of several human carcinomas such as breast, liver, colon and pancreas. However, little is known about the roles of this gene in lung cancer. Thus, we examined the involvement of HOTAIR in the development of NSCLCs. The expression of HOTAIR was examined in 77 NSCLCs and their corresponding normal lung tissues, and 6 metastatic lesions to brain by quantitative real-time RT-PCR. The high expression of HOTAIR (tumor/normal ratio &amp;gt; 2) was detected in 17 patients (22.1%) and was frequently found in patients with advanced stage, lymph node metastasis or lymphovascular invasion. The NSCLC patients with high expression of HOTAIR also showed significantly short disease free interval compared with those with low expression. Furthermore the metastatic lesions to brain demonstrated significantly higher HOTAIR expression than primary tissues. Accordingly, HOTAIR transfected A549 cells showed induced migration in vitro, and injected HOTAIR expressing cells into the tail vein of immunodeficient mice formed more metastases to liver or bone compared to empty vector transfected cells. We also found that the enhanced HOTAIR expression in lung cancer cells demonstrated the reduced expression of LAMB2 and LAMC3 both of which are downstream targets of PRC2. Taken together, these results might indicate that the evaluation of HOTAIR expression predict the poor outcome of NSCLC patients and that the overexpression of HOTAIR enhanced the aggressive biological behavior of NSCLC cells, at least in part, through the regulation of PRC2. Citation Format: Takayuki Nakagawa. Long noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free interval in human non-small cell lung 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 1836. doi:10.1158/1538-7445.AM2013-1836
Stereotactic Thrombosis of Intracranial Aneurysms
Authors: John F. Alksne
Journal: New England Journal of Medicine (1971)

Thirty-nine patients with intracranial aneurysms were treated stereotactically with a magnetic probe. Ten of 15 patients who were arousable without major neurologic deficit and who had an aneurysm of the anterior communicating or anterior cerebral artery had good results. Prognosis was particularly satisfactory if the aneurysm was less than 1 cm in diameter. Less favorable results were obtained when the aneurysm affected the internal carotid, or when patients were in Grade IV. Early angiographic study of patients with subarachnoid hemorrhage is essential if the method is to be used successfully in early cases.
Abstract 3345: Enhancer of zeste homolog 2 (EZH2) promotes expansion of breast tumor initiation cells through activation of Notch1-jagged signaling
Authors: Maria E. Gonzalez, Xin Li, Heather Kruger, Kathy Toy, Celina G. Kleer
Journal: Cancer Research (2011)

Abstract EZH2 is an oncogene which has been recently shown to regulate the differentiation of tissue specific stem cells. However the role of EZH2 on mammary stem cells is unknown. Notch1 signaling has been implicated in cell-fate determination of human mammary stem cells. We hypothesized that EZH2 may contribute to initiation and expansion of mammary stem cells through activation of Notch1 signaling. Methods: We developed two cell culture models: an inducible EZH2 up regulation system in MCF10A benign mammary cells and a lentivirus-mediated shRNA interference targeting EZH2 in SUM149 breast cancer cells. Mammary stem cells were identified using ALDH1+ and CD44+/CD24- by FACS. The effect of EZH2 on the tumorigenic ability of ALDH-1 positive and negative SUM149 cells was studied in a xenograft mouse model. Results: We found preferential expression of EZH2 in the stem cell population of normal primary breast cells compared to non stem cells. In MCF10A cells, EZH2 overexpression, (EZ-OV), was predominantly increased in the ALDH-1+ population. When we tested the role of EZH2 in the stem cell population we found that EZH2-OV increased the stem cell population of MCF10A cells while EZH2-KD decreased it in SUM149 cells. Microarray analysis identified Notch1-Jagged1 signaling as the most significantly downregulated targets of EZH2 in ALDH+ vs. ALDH- SUM149 cells. Consistently, EZH2-OV in MCF10A and primary breast cells increased Notch1 mRNA specifically in the ALDH1+ population. EZH2-OV increased Notch1 protein level and promoter activity in MCF10A cells. Mechanistically, Notch1 inhibition by GSI reversed the effect of EZH2-OV in the stem cell population of MCF10A cells. Our in vivo studies demonstrated that EZH2 KD in SUM149 cells decreased the growth of ALDH-1+ cells in xenograft experiments. Consistently, EZH2 KD tumors exhibited decreased Notch1 and Jagged1 protein levels. Conclusion: Collectively, these results indicate that EZH2 regulates mammary stem cells and requires, at least in part the activation of Notch1 signaling. 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 3345. doi:10.1158/1538-7445.AM2011-3345
Abstract 3437: A natural plant product to inhibit breast cancer metastasis
Authors: Namita Kundu, Xinrong Ma, Olga Goloubeva, Dawn Holt, Tyler Kochel, Amy M. Fulton
Journal: Cancer Research (2012)

Abstract In the United States, breast cancer death is the second leading cause of cancer deaths in women, primarily due to the occurrence of metastatic disease. We have identified a potential novel therapeutic agent derived from an edible root of the plant Colocasia esculenta, commonly known as taro, which has significant antimetastatic activity in a preclinical model of metastatic breast cancer and that should have minimal toxicity. We have shown for the first time that a water-soluble extract of taro (TE) potently inhibits lung colonizing ability (95-99%) as well as spontaneous metastasis from mammary gland-implanted tumors (85%), in a murine model of highly metastatic ER, PR and Her-2/neu negative breast cancer. TE modestly inhibits the proliferation of some, but not all, breast and prostate cancer cell lines and also causes morphologic changes including cell rounding. TE inhibits prostaglandin E2 (PGE2) levels and because PGE2 is a potent immune modulator, we examined the role of immunity in the therapeutic response to TE. We first examined the effect of TE on Natural Killer (NK) cell activities. TE modestly increases NK-mediated tumor cell lysis in vitro. We determined the effect of NK depletion on TE efficacy in vivo. The ability of TE to inhibit metastasis was modestly compromised in NK-depleted mice indicating that NK cells play a minor role in TE-mediated antimetastatic activity. To examine the role of T and B lymphocytes, TE efficacy was examined in Balb/c SCID mice. Antimetastatic activity of TE was completely lost in SCID mice lacking mature T and B cells. Thus, T and /or B cell functions contribute to the mechanism by which TE inhibits metastasis. In published studies we have identified the active component of TE as one of three closely related taro proteins, tarin, taro lectin and 12-kDa storage protein. Current studies are determining how these candidate proteins affect immune functions to inhibit breast cancer metastasis. 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 3437. doi:1538-7445.AM2012-3437
P724Association of biochemical markers with long-term outcomes in patients after coronary angioplasty and stenting
Authors: NA Musikhina, TI Petelina, LI Gapon, VA Kuznetsov, AG Takkand, None Osipova
Journal: Cardiovascular Research (2014)

Purpose: To perform a prospective comparative analysis of lipid profiles, markers for inflammation and endothelial dysfunction in groups of coronary artery disease (CAD) patients with and without episodes of unstable coronary blood flow after percutaneous coronary intervention (PCI); and to detect factors which may be used as predictors of cardiovascular complications. Methods: A total of 95 patients aged 60.47±9.54 years with CAD and stable angina were divided into two groups. Group 1 included patients with CAD without episodes of unstable coronary blood flow after PCI (n=77) and group 2 included CAD patients with episodes of unstable coronary blood flow after PCI (n=18). All patients were matched by age, CAD duration, diabetes mellitus, blood pressure levels and smoking history. Results: Laboratory tests were performed before PCI and 12±2.4 month after. The level of lipoprotein (a), HDLC, FNO-a equally decreased in both groups. In patients of group 2 compared to group 1 there were observed significantly increased levels of atherogenic indices of the lipid profile (total cholesterol, LDL) and inflammation markers: high-sensitivity C-reactive protein, homocysteine, levels of soluble CD40 ligand (CD40L), interleukin-1β interleukin- B6, and decreased levels of nitrites. Significant correlations of inflammatory markers and endothelial dysfunction with body-weight index, family history of CAD, significant multivessel stenosis, number of angina attacks per week and presence of diabetes mellitus were revealed in group 2. Multivariate logistic regression analysis revealed that patients with unstable angina at baseline had the risk of unstable coronary blood flow after PCI 4 times higher (p=0.02). Conclusion: The inflammatory markers: C-reactive protein, homocysteine, CD40L can initiate unstable coronary blood flow after coronary angioplasty and stenting.
Local control with conventional and hypofractionated adjuvant radiotherapy for ductal carcinoma in-situ: is there a difference in outcome?.
Authors: D Williamson, S Fung, M Pintilie, R Dinniwell, A Fyles
Journal: Cancer Research (2009)

Abstract Abstract #1162 Purpose&amp;#x2028; Trials of adjuvant whole breast radiotherapy (WBRT) following breast-conserving surgery for invasive breast cancer indicate equivalent efficacy and morbidity for conventional and hypofractionated treatment. WBRT for ductal carcinoma in-situ (DCIS) improves local control, however an optimal dose fractionation remains undefined. Our group policy allowed for the use of both schedules, therefore we compared local control in women with DCIS following breast-conserving surgery.&amp;#x2028; Methods&amp;#x2028; Two hundred and sixty six patients treated between January 1999 and December 2004 with conventional (50 Gy/25 fractions) or hypofractionated (42.4 Gy/16 daily fractions or 40 Gy/16 fractions + 12.5 Gy/5 fraction boost) radiotherapy schedules to the whole breast after breast-conserving surgery for DCIS were identified and retrospectively reviewed. Treatment schedules were evaluated for outcomes in terms of ipsilateral breast recurrence.&amp;#x2028; Results&amp;#x2028; The median age at diagnosis 56.7 years (range 32.2-83.8 years), and 82% (218 patients) presented with mammographic abnormality. Median tumour size was 1.5 cm (range 0.4-10 cm), grade 3 tumours were present in 105 women (39%), and comedonecrosis in 145 (55%). Fifty-one patients (19%) had multifocal disease. Median follow-up was 45.1 months (range 0.7-106.8 months). Prognostic features were well matched in both groups.&amp;#x2028; One-hundred and four patients (39%) were treated with conventional and 162 (61%) with hypofractionated WBRT. There were a total of 14 confirmed local recurrences in the previously radiated breast. Six recurrences occurred in the 104 (5.8%) patients treated with a conventional schedule and 8 of 162 (4.9%) patients treated with a hypofractionated schedule. Actuarial risk of recurrence at 4 years was 7% with hypofractionated WBRT and 5% with a standard schedule (p=0.85).&amp;#x2028; &amp;#x2028; Eight patients recurred with DCIS and 6 with invasive carcinomas, all 14 were treated surgically with adjuvant treatment as indicated clinically, 1 patient with clinical recurrent disease refused biopsy and further conventional treatment. Univariate analysis showed a trend to increased risk of recurrence with grade 3 tumours (10% at 4 years vs. 3% for grade1/2, p=0.053) and presence of comedonecrosis (8% vs. 2%, p=0.096), but not multi-focal disease (7% vs. 5%, p=0.78).&amp;#x2028; Conclusions&amp;#x2028; Hypofractionated adjuvant WBRT schedules following breast-conserving surgery for DCIS have comparable local control rates to a conventional radiation schedule. Hypofractionated WBRT is more convenient for patients, has equivalent morbidity and should be considered in this patient group. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1162.
THE EFFECT OF DRUG-COATED BALLOON ANGIOPLASTY FOR IN-STENT RESTENOSIS EVALUATED BY SERIAL ANGIOSCOPY AND OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Naotaka Akutsu, Tadateru Takayama, Takashi Mineki, Takaaki Kougo, Nobuhiro Murata, Korehito Iida, Toshihiko Nishida, Tooru Oshima, Hironori Haruta, Daisuke Fukamachi, Takafumi Hiro, Atsushi Hirayama
Journal: Journal of the American College of Cardiology (2016)