tbuckley/cabot-search huggingface dataset:
Abstract LB-292: NANOG promotes chemoresistance in prostate carcinoma cells
Authors: Hongmei Jiang, Man-Tzu Wang, Daotai Nie
Journal: Cancer Research (2012)

Abstract NANOG promotes chemoresistance in prostate carcinoma cells Hongmei Jiang, Man-Tzu Wang, Daotai Nie The emergence of drug resistant prostate cancer cells is a leading cause of chemotherapy failure in patients with prostate cancer. The mechanisms behind the acquisition of chemoresistance in prostate cancers are, however, poorly understood. NANOG is a transcription factor associated with the self-renewal of embryonic stem cells. Expression of NANOG has been detected in a number of cancer cells, and its expression linked with those positive for stem/progenitor markers. In the present studies, several lines of evidence are presented to suggest that NANOG regulates tumor responses to chemotherapy. First, in the surviving fractions of tumor cells after chemotherapy, there was an elevated level of NANOG expression and activities. Second, prospective enrichment of tumor cells with endogenous NANOG expression led to enrichment of tumor cells resistant to taxol, vinblastine, and doxorubicin. Knockdown of NANOG expression via small hairpin RNAs (shRNAs) sensitized tumor cells toward chemotherapeutics. Real-time PCR array identified an enhanced expression of the ATP-binding cassette efflux transporter B1 (ABCB1) and G2 (ABCG2) in tumor cells enriched with endogenous NANOG expression. Inhibition of ABCB1 activities or knockdown of ABCB1 expression attenuated, but not abolished, the increased resistance in NANOG expressing cells toward taxol and vinblastine. Knockdown of ABCG2 attenuated the resistance of NANOG-expressing tumor cells toward doxorubicin. Together, our results suggest that NANOG confers tumor cells with increased resistance to chemotherapy partially through regulating the expression of ABC transporters. 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 LB-292. doi:1538-7445.AM2012-LB-292
Abstract 473: CD4+ T cell help differentially influences anti-tumor immunity as a function of T cell avidity
Authors: Ziqiang Zhu, Vinod Singh, Vincenzo Bronte, Lionel Feigenbaum, Arthur Hurwitz
Journal: Cancer Research (2011)

Abstract One of the major hurdles for cancer immunotherapy is that most tumors express self-antigens to which the immune system is unresponsive due to self-tolerance. Our lab and others have demonstrated that high-avidity tumor-specific CD8+ T cells are superior in anti-tumor activity to low avidity T cells. However, adoptive transfer of high-avidity, tumor-specific CTL populations may fail due to loss of CTL effector functions upon tumor infiltration. Therefore, strategies to maintain effector functions of high avidity CTL, or enhancement of low avidity CTL are desirable. To investigate whether provision of CD4+ T cell help will enhance the effectiveness of high-avidity CTLs in anti-tumor immunity as compared to lower avidity T cells, we utilized two transgenic mouse lines developed in our lab that bear different TCR transgenes specific for a common melanoma differentiation antigen, tyrosinase-related protein 2 (TRP-2(180-188)). T cells from clone 24 TCR Tg mice (TCRhi) show higher avidity than those from clone 37 (TCRlo) mice based on tetramer dissociation and in vitro effector function assays. Here we report that co-activation of CD4+ T cells (OVA323-339 specific, CD4-OVA) with TRP-2-specific CD8+ T cells can boost the in vitro function of TCRhi cells, including proliferation, IFN-γ secretion, Gr-B secretion as well as cell-mediated cytotoxicity, but had minimal effect on TCRlo cells. We observed that only adoptive co-transfer of CD4-OVA cells with TCRhi cells suppressed tumor growth of (5 day) established B16 melanoma tumors. Furthermore, those mice receiving co-transferred CD4-OVA cells with TCRhi cells developed autoimmune depigmentation at the sites of vaccination and tumor challenge. Our finding may have important implications for enhancement of cancer immunotherapy. 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 473. doi:10.1158/1538-7445.AM2011-473
Abstract PD06-08: Size Matters: Incorporation of Sentinel Lymph Node (SLN) Metastasis Size into a Nomogram Predicting NonSLN Involvement in SLN Positive Breast Cancer Patients
Authors: EA Mittendorf, JC Boughey, AC Degnim, R Harrell, R Bassett, M Yi, F Meric-Bernstam, MI Ross, GV Babiera, HM Kuerer, A Lucci, I Bedrosian, KK Hunt, RF. Hwang
Journal: Cancer Research (2010)

Abstract Purpose: Emerging data from cooperative group trials suggests that not all patients with a positive SLN require completion axillary lymph node dissection (ALND). The controversy regarding who will benefit from additional nodal clearance continues, suggesting a need for improved tools to predict non-SLN involvement. We hypothesized that the size of a SLN metastasis evaluated as a continuous variable would be an important predictor of non-SLN involvement. The goal of this study was to determine clinicopathologic factors including SLN metastasis size that predicted non-SLN involvement and to use these factors to construct an improved predictive nomogram. Methods: Using a prospective database, we identified 509 patients with invasive breast cancer from 1996 - 2007 with a positive SLN who underwent ALND. Patients receiving neoadjuvant therapy were excluded. Clinicopathologic data including age, primary tumor size, presence of multifocal disease, histology (invasive ductal vs. invasive lobular vs. mixed invasive), tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status, presence of lymphovascular invasion (LVI), the number of SLNs identified, number of positive SLNs, the maximum SLN metastasis size and the presence of extranodal extension were recorded. For SLNs described only as containing isolated tumor cells, size was recorded as 0.1 mm. Univariate and multivariate logistic regression analyses were performed to identify factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients. Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (p&amp;lt;.001), number of positive SLN (p&amp;lt;.001), maximum SLN metastasis size (p&amp;lt;.001), extranodal extension (p&amp;lt;.001), primary tumor size (p=.001), LVI (p=.019) and histology (p=.034). On multivariate analysis, all factors remained significant at the 5% level except LVI. A nomogram was created using these variables. When applied to an external cohort, the nomogram was accurate and discriminating with an area under the receiver operating characteristic curve of .73 (95% CI: .68 - .77). Conclusions: SLN metastasis size is predictive for identifying additional disease in the axilla. These data have been incorporated into a nomogram that accurately predicts the likelihood of having additional, non-SLN metastasis suggesting that routine reporting of the SLN metastasis size would assist with clinical decision making regarding the need to perform a completion ALND. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-08.
OP0299-HPR The Evaluation of A Patient Decision AID for Anti-Rheumatic Drugs
Authors: I. Nota, C. Drossaert, E. Taal, M. van de Laar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Research among Dutch arthritis patients has shown that quality improvement is needed in the field of “information about medication and treatment” and that patients want to be more involved in treatment decision-making. To educate patients about Disease Modifying Anti-rheumatic Drugs (DMARDs) and to increase patient involvement in decision making about medication, a Patient Decision Aid (PtDA) was developed. For the development a user9s centred design procedure was used. <h3>Objectives</h3> Aim of the current study was to evaluate the usage, patients9satisfaction about, and a the effects of the PtDA. <h3>Methods</h3> A quasi-experimental questionnaire study among arthritis patients who were facing the decision to start (a different) drug, received a referreal to the PTDA (intervention group, n=123) or not (control group (n=158) A questionnaire was sent to all patients, 6 weeks after inclusion. The questionnaire included questions on, among others, patient9s perceived role, knowledge, and satisfaction with the decision process. Patients from the intervention group were also questioned about the use of the PtDA, its perceived usefulness, its perceived ease of use, and its perceived effectiveness. <h3>Results</h3> The PtDA was used by 57% of respondents in the intervention group. Younger (p=0.003) and higher educated (p=0.004) patients were more likely to have used the PtDA. Users were on average very positive about the PtDA: they rated the PtDA as useful, easy to use and easy to understand. Compared to the control group, patients in the intervention group perceived a more active role in decision-making (p=0.01) and perceived the final choice to be more consistent with their personal values (p=0.02). A significant increased knowledge was revealed among users of the PtDA (p=0.03). No effects were found on satisfaction, trust in physician, beliefs about medication, or adherence to medication. <h3>Conclusions</h3> Our PtDA can be a valuable aid in improving patient participation in medical decision-making about anti-rheumatic drugs. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5030
Abstract 1107: Mutant p53 increases epithelial mesenchymal transition, estrogen receptor alpha and erbB2/Her2/neu
Authors: Mary Strasberg- Rieber, Manuel Rieber
Journal: Cancer Research (2010)

Abstract OBJECTIVES.- Progression of carcinomas involves transition from an epithelial cobblestone-like cytoarchitecture to an elongated, mesenchymal phenotype., leading to an epithelial to mesenchymal transdifferentiation (EMT) (1). Since the p53 tumor suppressor pathway is inactivated in most human cancers due to gene mutations or dysfunction, we now investigated in human wt p53 breast carcinoma cells, whether EMT and cell proliferation are influenced by introducing a dominant-negative (DN) R175H mutant p53 (2). This mutation occurring in the p53 zinc-binding domain, is common to breast cancer patients poorly responsive to therapy (2) METHODS.- .- Fluorescence microscopy was used to determine EMT-linked decreases in E-cadherin and cytokeratin 18. These changes and others associated with EMT, were verified by immune blotting. Laser scanning cytometry was used to measure expression of ErbB2 and estrogen receptor alpha, cell cycle profile and proliferation (2). RESULTS.- Cells transduced with the DN-R175H mutant p53, increased expression of the mesenchymal marker vimentin and proliferation-associated cyclin A, also showing a greater G2 population which correlated with increased c-neu/Her2/ErbB2. Joint cytometric analysis of the Ki67proliferation marker and estrogen receptor alpha revealed a greater number of estrogen receptor-positive proliferating cells (3) among the mesenchymal population harbouring the DN-R175H mutant p53 .CONCLUSIONS.- These results suggest that EMT induced by the DN-R175H mutant p53 promotes a gain of pro-oncogenic function by increasing the % of proliferating cells expressing estrogen receptor alpha (3) and the expression of erbB2 (4) REFERENCES 1.-Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009 119: 1420-8. 2.- Rieber M, Strasberg Rieber M. DN-R175H p53 mutation is more effective than p53 interference in inducing epithelial disorganization and activation of proliferation signals in human carcinoma cells : role of E-cadherin. Int J Cancer. 2009; 125:1604-12. 3.- Shoker BS, Jarvis C, Clarke RB, Anderson E, Hewlett J, Davies MP, Sibson DR, Sloane JP. Estrogen receptor-positive proliferating cells in the normal and precancerous breast. Am J Pathol 1999, 155:1811-1815. 4.- Cicalese A, Bonizzi G, Pasi CE, Faretta M, Ronzoni S, Giulini B, Brisken C, Minucci S, Di Fiore PP, Pelicci PG. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell. 2009; 138:1083-95. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1107.
PTH-179 An Audit of Clinical outcomes of Sehcat Study in Patients with Chronic Diarrhoea: Abstract PTH-179 Table 1
Authors: L Kumar, B Jamshed, A Emmanuel
Journal: Gut (2013)

<h3>Introduction</h3> Latest NICE guidance suggest that there is not enough evidence to determine whether SeHCAT test is a cost effective option for diagnosing bile acid malabsorption (BAM) among people with IBS-D and Crohn's disease patients without ileal resection. We undertook an audit of sequential patients referred for SeHCAT testing to assess diagnostic value. <h3>Methods</h3> Retrospective data was collected from 88 consecutive patients referred to Nuclear Medicine for SeHCAT testing over one year. The indication for the test request and treatment given were collected from request forms, clinic letters and GP record. Subjective global outcome was assessed at mean of 3 months after treatment (range 2–7). <h3>Results</h3> Of 88 patients who underwent SeHCAT test, 49 (56%) were found to be positive for bile acid malabsorption. Of these 29 (59%) had severe <i>(</i>&lt;<i> 5% retention)</i>, 9 (18%) had moderate <i>(</i>&gt;<i> 5 and</i> &lt;<i> 10% retention)</i> and 11 (22%) had mild BAM <i>(</i>&gt;<i> 10 and</i> &lt;<i> 15% retention)</i>. With regard to the distribution of positive SeHCAT test results according to aetiology, there were 18 patients who fell into BAM Type 1 (Ileal disease/resection) group out of which 17(94%) were positive. Type 2 (Idiopathic BAM) had a total of 57 patients out of which 24(42%) were positive and Type 3 (Secondary to other GI disease) had 13 patients of which 8(62%) tested positive to SeHCAT study. Table 1 below shows the outcomes of bile acid sequestrant (BAS) according to BAM groups. 39/88 (44%) patients had a negative test. Diagnoses were made as follows: IBS-D 13, inflammatory bowel disease with no BAM 8, functional or non-specific diarrhoea 18. In these patients BAS was empirically started, in spite of the test results, in 6, 2 and 5 patients respectively. Only 1 of these 13 (8%) patients (who had IBS-D) improved. <h3>Conclusion</h3> Changes in treatment as a result of the SeHCAT test were made in 70% (62/88) of all patients: 84% (41/49) positive patients and 33% (13/39) negative patients. In terms of yield of SeHCAT, patients with chronic diarrhoea and ileal disease (BAM Type 1) may warrant empiric BAS treatment without testing since there was 94% response, suggesting limited value in terms of yield of new information. In contrast, there was value to a negative study, which predicted lack of response (8%) to BAS. <h3>Disclosure of Interest</h3> None Declared.
Politicians urge health department to consider over-ruling EU law to tackle drug shortages in UK
Authors: A. O'Dowd
Journal: BMJ (2012)

MPs and peers have called on the government to consider over-ruling European Union law to tackle the growing problem of shortages of drugs in the United Kingdom, which is adversely affecting the care of patients.

A shortage of some NHS prescription drugs has been a problem in the UK for the past four years and is getting worse, says a new report from the parliamentary All Party Pharmacy Group.

The effects have been felt by some patients with conditions such as epilepsy, schizophrenia, and diabetes because they have not been able to get essential drugs when needed.

The All-Party Pharmacy Group, which comprises MPs and peers from the three main political parties, carried out a six month inquiry into drug shortages.

In its report, published on 15 May, the group found that shortages have been caused principally by the export of drugs …
PWE-194 We've got to the caecum…now what will we do with the polyps?
Authors: R Bevan, T Lee, M Warren
Journal: Gut (2012)

Introduction Recent work, especially in the national Bowel Cancer Screening Programme (BCSP) has focussed on adenoma detection and removal as a marker of quality of colonoscopy. It is vital that this quality assurance is applied to all patients undergoing colonoscopy and that we move away from caecal intubation rate (CIR) as the main marker of a successful colonoscopy. We aimed to review practice in terms of adenoma detection and removal technique among all NHS colonoscopist in a busy district general hospital. Methods Procedural data were retrospectively collected from Endosoft reporting software for all colonoscopies performed in a 6-month period. BSCP lists were excluded. The reports were reviewed and data collected including operator, size of list, extent of procedure, and details of polyps found—size, location, description, whether removed or biopsied, method of removal and if tattoo used. In addition, the completeness of the report was recorded. Where polyps were removed, the histology result was also recorded. Results 472 procedures were performed by 18 operators—three trainees, two nurse endoscopists, and 13 consultants (eight gastroenterology, five surgical). 159 procedures identified polyps (246 polyps in total), with a unit polyp detection rate of 33.7%. Individual polyp detection rates varied between 14.7% and 58.8%. Histology showed a unit adenoma detection rate (ADR) of 21%. Eight cancers and one polyp cancer were detected. Documentation of polyp location was good (240/246) but size and description were less well documented (171 and 185 out of 246 respectively). 211 polyps were removed, 31 left in situ, and unclear in 4. 26 polyps removed were ≥10 mm, of which nine with a snare and 16 by EMR (one unknown.) Smaller polyps were removed by a variety of methods ([Abstract PWE-194 table 1][1]). View this table: Abstract PWE-194 Table 1 Polypectomy methods Conclusion ADR in this unit is comparable to elsewhere in the UK, but not as high as within the BCSP, although this represents a different patient population. Documentation of these polyps varied greatly, and could be improved. Detection rate and removal methods varied widely between endoscopists. This prompted the creation of an “aide memoir” poster (see [Abstract PWE-194 figure 1][2]) to be displayed in the endoscopy room, advising on documentation and highlighting the current guidance for management of polyps. Teaching was also undertaken at dedicated “polypectomy afternoons,” with a view to re-assessing polyp management at a later date, using ADR as quality marker. ![Abstract PWE-194 Figure 1][3]</img> Abstract PWE-194 Figure 1 Competing interests None declared. [1]: #T1 [2]: #F1 [3]: pending:yes
P3-03-03: Congruence between Patterns of microRNA Expression and Histologic Grading of Invasive Breast Carcinomas.
Authors: DL Ellsworth, DT Croft, LA Field, B Deyarmin, J Kane, RE Ellsworth, JA Hooke, CD Shriver
Journal: Cancer Research (2011)

Abstract Background Histologic grading may be used as an indicator of prognosis in breast cancer; patients with low-grade carcinomas have ∼85% ten-year survival compared to just 45% survival in patients with high-grade disease. Although useful for risk stratification, assigning nuclear grade is subjective, and a large proportion of carcinomas are classified as intermediate-grade with uncertain prognosis, thus limiting clinical utility. MicroRNAs (miRNAs) regulate gene expression and serve an important role in breast cancer development. In this study we examined miRNA expression profiles in low-grade and high-grade breast carcinomas to determine if miRNA expression is associated with pathological classifications of tumor grade. Methods: Breast tumors were obtained from 69 patients enrolled in the Clinical Breast Care Project. Samples were partitioned into low-grade (n=30) or high-grade (n=39) categories using the Nottingham Histologic Score. Following laser microdissection of frozen tissue sections, miRNA was isolated from pure populations of breast tumor cells and hybridized to Affymetrix GeneChip® miRNA arrays containing over 800 human miRNA probes. Expression profiles were analyzed with Partek Genomics Suite using the miRNA Expression Module. Results: We identified 30 unique miRNAs that showed differential expression at a False Discovery Rate (FDR) p&amp;lt;0.05 between low-grade and high-grade breast carcinomas. Gene targets for these miRNAs function primarily in metabolism and cell communication. Expression of hsa-miR-18a and hsa-miR-572 was significantly different between histologic grades at an FDR p&amp;lt;1×10−8 and hierarchical clustering based on these miRNAs correctly classified 97% (29/30) of low-grade and 90% (35/39) of high-grade tumors. miR-18a has been shown to inhibit ER signaling and promote cellular differentiation, while the role of miR-572 in breast carcinogenesis is not well known. Conclusions: Dysregulation of miRNAs may accompany changes in cellular morphology typically used in histologic classification of breast carcinomas. Patterns of miRNA expression may improve reproducibility and clinical utility of tumor grading and may prove useful for prediction of recurrence and survival for patients with intermediate-grade carcinomas. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-03.
Association between Prior Cytomegalovirus Infection and the Risk of Restenosis after Coronary Atherectomy
Authors: Yi Fu Zhou, Martin B. Leon, Myron A. Waclawiw, Jeffery J. Popma, Zu Xi Yu, Toren Finkel, Stephen E. Epstein
Journal: New England Journal of Medicine (1996)

Restenosis occurs commonly after coronary angioplasty and atherectomy, but the causes of restenosis are poorly understood. Recently, it has been found that cytomegalovirus (CMV) DNA is present in restenotic lesions from atherectomy specimens. This and other evidence suggest that CMV may have a role in the process of restenosis.We prospectively studied 75 consecutive patients undergoing directional coronary atherectomy for symptomatic coronary artery disease. Before atherectomy was performed, we measured blood levels of anti-CMV IgG antibodies to determine whether previous exposure to CMV increased the risk of restenosis, as determined by coronary angiography performed six months after atherectomy.After atherectomy, the mean (+/- SD) minimal luminal diameter of the target vessel was greater in the 49 patients who were seropositive for CMV than in the 26 patients who were seronegative (3.18 +/- 0.51 mm vs. 2.89 +/- 0.45 mm, P=0.01). After six months, however, the seropositive patients had a greater reduction in the luminal diameter (1.24 +/- 0.83 mm vs. 0.68 +/- 0.69 mm, P = 0.003), resulting in a significantly higher rate o restenosis in the seropositive patients (43 percent vs. 8 percent, P = 0.002). In a multivariable logistic-regression model, CMV seropositivity and the CMV titer were independently predictive of restenosis (odds ratios, 12.9 and 8.1, respectively). There was no evidence of acute infection, since the titer of anti-CMV IgG antibodies did not increase over time and tests for anti-CMV IgM antibodies were negative in all patients.Prior infection with CMV is strong independent risk factor for restenosis after coronary atherectomy. If confirmed, these findings may help identify patients at risk for restenosis.