tbuckley/cabot-search huggingface dataset:
Abstract 326: Investigation of molecular subtypes within FFPE breast cancer tumors using the Breast Cancer DSA®
Authors: Steve Deharo, Jude M. Mulligan, Fionnuala A. McDyer, Max Bylesjo, Iris Halfpenny, Thomas Delaney, Jennifer E. Quinn, Fergus J. Couch, Vitali Proutski, Paul D. Harkin, Richard D. Kennedy
Journal: Cancer Research (2011)

Abstract Microarray gene expression profiling has facilitated identification of molecular subtypes which can be associated with disease outcome and treatment response. However current platforms lack disease focus, potentially missing vital information contained in patient tissue samples. Moreover, a wide range of FFPE sample cohorts are available but their use is limited by the mRNA degradation inherent to the sample fixation process. By combining the Breast Cancer DSA® with powerful data analysis methodology, we reproduced the five major molecular subtypes in breast cancer based on a cohort of 107 FFPE samples. Furthermore, we showed that the established subtypes do not extend to BRCA1 and BRCA2 mutant tumours, necessitating expansion of the original breast cancer subtypes definition. Following RMA pre-processing of the 107 raw profiles, the data was transformed to overcome the association between profile quality and expression variability. If left untreated, this technical variability, often observed with FFPE tissues, can impair the study of inherent biological variations. Using the intrinsic list of 277 genes previously identified as differentiating breast cancer subtypes in fresh frozen samples [Sorlie et al., 2003], initially the sporadic samples were examined using hierarchical agglomerative clustering. All five original subtypes were identified, verifying the ability to detect subtypes in FFPE samples using the breast cancer DSA®. When the intrinsic list was applied to all 107 samples including BRCA1 and BRCA2 mutant samples, the subtypes were still distinguishable, although 31% of the mutant tumors were unclassified suggesting that specific biological processes defining BRCA1/BRCA2 mutant tumours are not captured by the original breast cancer molecular classification. We have successfully overcome the limitation imposed by FFPE sample microarray profiling by using the Breast Cancer DSA® and advanced data manipulation and exploration to reproduce molecular subtypes previously identified using fresh frozen samples. Further investigation to extend the previously identifed subtypes will progress the investigation of the heterogeneous biology underlying breast cancer. 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 326. doi:10.1158/1538-7445.AM2011-326
Point process models in asthma attacks for assessing environmental risk factors.
Authors: T Kamakura, T Yanagimoto
Journal: Environmental Health Perspectives (1985)

Point process models are reviewed and discussed for assessing the effects of environmental risk factors on asthma attacks. It is pointed out that the logit model and proportional intensity model are useful for analyzing the data based on the diaries recorded consecutively during several months or during a few years. Some covariates that seems to influence upon asthmatics are explored using these models. Further work on estimating the smoothed base-line intensity function is briefly discussed in terms of the Bayes model.
LB-005 Post-infection Dysbiosis – A Potential Cause Of Irritable Bowel Syndrome?
Authors: M Acres, S Owen, R Rigby
Journal: Gut (2014)

<h3>Introduction</h3> Gut microflora plays an important role in the normal function of the human intestine. A shift in the normal gut flora, termed dysbiosis, has an impact on many health aspects including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBS is characterised by abnormal gastrointestinal motility associated with psychosocial factors. Increasing evidence supports a role of dysbiosis in the pathophysiology of IBS, potentially through the impact of microflora on neuroendocrine pathways. Anecdotal evidence suggests that onset of symptoms of IBS are associated with an episode of gastroenteritis, which ostensibly may cause a shift in the intestinal microflora. We therefore sought to establish whether there is an association between historical gastroenteritis (caused by <i>Salmonella enteritidis </i>or <i>Campylobacter jejuni</i> infection) and IBS occurrence. <h3>Methods</h3> Indirect ELISA was used to measure levels of IgA and IgG to <i>Campylobacter jejuni </i>and <i>Salmonella enteritidis </i>in 90 patients, either with IBS (30), IBD (30) and controls (30). Data was analysed using appropriate statistical tests to establish whether antibody levels were significantly raised in IBS patients. <h3>Results</h3> We will determine whether IgG and/or IgA serum antibodies are elevated in the three patient groups. ELISA detection techniques have been optimised and data collection is still in progress, results have yet to be unblinded. Results will be available and discussed at the meeting. <h3>Conclusion</h3> This study explores the impact of dysbiosis on intestinal health and wellbeing. If post-infectious dysbiosis is associated with IBS, this may provide a rationale for changes to the treatment of IBS. <h3>Disclosure of Interest</h3> None Declared.
Herpes Labialis and Facial-Nerve Paralysis
Authors: E Peter Park, Brian C Boulmay
Journal: New England Journal of Medicine (2014)

A 65-year-old woman presented to the emergency department with odynophagia, facial edema, and perioral swelling with crusting blisters containing clear fluid. One week earlier, she had completed one cycle of treatment with rituximab and bendamustine for CLL.
Abstract LB-380: Distinct methylation pattern in early-onset colorectal cancer patients without detectable germline mutation
Authors: Tsun-Leung Chan, Carmen Li, Siu-Tsan Yuen, Anthony KW Chan, Wendy WY Tsui, Annie SY Chan, Suet-Yi Leung
Journal: Cancer Research (2012)

Abstract Colorectal cancer (CRC) is currently the second most common cancer and mortality rate of all cancers in Hong Kong. We have previously reported a higher incidence of early-onset colorectal cancer patients compare with other ethnic groups, which may be caused by genetic or epigenetic predisposition in the Chinese population. Despite we confirmed Lynch Syndrome (LS) plays a significant role in it, pathogenic event of roughly 20% of young patients with MSI tumour cannot be identified. These patients are still susceptible to novel genetic or epigenetic predisposition of CRC. In this study, we compared the epigenetic signature of CRC patients below and above the age of 50 years old, who developed High level of microsatellite instability (MSI-H) and loss of MLH1 expression. The CpG island methylator phenotype (CIMP), regional methylation events, Braf and Kras mutation status have been examined. Among 12 cases of the early-onset patients, unexpectedly 5 of them showed constitutive MLH1 promoter hypermethylation versus 1 in 26 cases of the late-onset control patients by pyrosequencing (p-value &amp;lt; 0.01). CIMP-High status, which has been frequently reported in late-onset patients, was found to be 25% and 77% in the early and late-onset groups respectively (p value &amp;lt; 0.001). Strikingly, regional methylation coincides with the CIMP-High cases and MLH1 promoter methylation was the unique epimutation event in the chromosomal region encompass MLH1 in most of the early-onset patients. We are the first to demonstrate that CIMP status and MLH1 regional methylation are a distinct phenotype in the patient with early-onset CRC irrespective of the constitutive status of MLH1 promoter methylation event. Our data suggest that the tumorigenesis of early-onset CRC is significantly different from patients with late-onset CRC despite they are all classified as MSI-H and loss of expression of MLH1. Lastly, epigenetic signature of most of the early-onset CRC patients is indistinguishable from the patient with constitutive MLH1 promoter methylation. It is unclear epigenetic predisposition contribute to the high incidence of early-onset CRC. Further investigation for additional markers should be performed as routine Kras and Braf mutation status were uninformative. 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-380. doi:1538-7445.AM2012-LB-380
O104 CYTOLYTIC EFFECTOR FUNCTIONS PREDOMINATE IN CD8+ T-CELL AND NK-CELL MEDIATED INHIBITION OF VIRAL REPLICATION IN HBV INFECTED HEPATOCYTES OVEREXPRESSING SODIUM TAUROCHOLATE COTRANSPORTING POLYPEPTIDE
Authors: A. Hoh, Y. Ni, A. Bertoletti, S. Urban, R. Thimme
Journal: Journal of Hepatology (2014)
Abstract 2379: Cyclin D3 is important for ErbB2-induced mammary cancer initiation and progression in the absence of Cyclin D1
Authors: Qian Zhang, Kazuhito Sakamoto, Aleata A. Triplett, Wan-chi Lin, Bradley A. Creamer, Kay-Uwe Wagner
Journal: Cancer Research (2011)

Abstract The cell cycle regulatory protein Cyclin D1 has been reported to be essential for both normal mammary gland development during pregnancy and the malignant transformation of the mammary epithelium in response to receptor tyrosine kinase (RTK) signaling. We have recently reported that the prolactin receptor-associated kinase Jak2 controls the transcriptional activation and, more importantly, the nuclear accumulation of Cyclin D1 in normal mammary epithelial cells via expression and activation of Akt1. We also demonstrated that the functional ablation of Jak2 and Stat5 in ErbB2-expressing mammary epithelial cells protects against the onset of mammary tumorigenesis. Jak2, however, is not required for the survival and proliferation of neoplastic cells. The constitutive activation of ErbB2 signaling, which is an initial event in the formation of mammary cancer in this model, was able to override the functional role of Jak2 in regulating the expression of Akt1 and Cyclin D1. To further define the role of the downstream effector Cyclin D1 during cancer initiation and progression in response to Jak2 and RTK signaling, we generated an ErbB2-associated mammary cancer model that allows a functional ablation of Cyclin D1 either prior to or following neoplastic transformation. Surprisingly, and in sharp contrast to previous reports, nearly all Cyclin D1-deficient females expressing wildtype ErbB2 developed mammary tumors. While Cyclin D1 deficiency extended the tumor-free survival, this particular cell cycle regulatory protein was clearly not required for tumor maintenance and progression. Growth and proliferation of the vast majority of Cyclin D1-deficient primary mammary cancers was accompanied by an upregulation of Cyclin D3. Since Cyclin D2 expression remained very low, knocking down the last remaining D-type cyclin (i.e. Cyclin D3) in tumor-derived primary cancer cells using three different shRNA constructs was sufficient to attenuate the proliferation rates. Interestingly, the ablation of the pool of all three D-type cyclins did not result in an upregulation of Cyclin E. Collectively, the results of this study show that Cyclin D1 is dispensable for neoplastic transformation of mammary epithelial cells and it might therefore not serve as a sole therapeutic target to treat ErbB2-associated breast cancers as previously suggested. In addition, these observations indicate that Cyclin D1 is most likely not the only downstream effector of Jak2 signaling that mediates the protective effects of a functional ablation of Jak2 in ErbB2-induced mammary carcinogenesis. 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 2379. doi:10.1158/1538-7445.AM2011-2379
Abstract 2547: Quantification of Myocardial Perfusion in Patients Using 256-Row Multidetector Computed Tomography: Evaluation of Endocardial vs. Epicardial Blood Flow
Authors: Richard T George, Omair Yousuf, Kakuya Kitagawa, Hyuk-Jae Chang, David A Bluemke, Albert C Lardo, Joao A Lima
Journal: Circulation (2007)

Introduction: The advent of 256x0.5 mm high resolution multidetector computed tomography (MDCT) created the potential to quantify subendocardial myocardial blood flow (MBF) reduction, the hallmark of ischemia. The purpose of this study was to test the hypothesis that adenosine stress / rest 256x0.5mm MDCT can detect ischemia by measuring differences in subendo-cardial versus subepicardial MBF. Methods: Nineteen patients with abnormal SPECT perfusion studies underwent adenosine (140μg/kg/min) stress 256x0.5mm MDCT perfusion imaging (CTP): 120kV, 100mAs, 3 gantry rotations at 0.5 secs, followed by rest 256x0.5mm MDCT angiography (CTA): 120kV, 175mAs, 3 gantry rotations at 0.5 secs. CT perfusion images were reconstructed in the short axis with a 3 mm slice thickness. Endocardial and epicardial borders were defined, myocardium was sectored according to the standard 17 segment model, and divided circumferentially into endocardial and epicardial layers. The transmural perfusion ratio (TPR) was calculated by dividing the endocardial attenuation density (AD) by the epicardial AD in each sector. Ischemia was defined as TPR &lt;0.8 in more than one sector. The TPR results were compared to the presence or absence of stenoses ≥50% on CTA and perfusion deficits on SPECT. Results: Mean TPR in abnormal and normal sectors was 0.71±0.05 and 1.01±0.06, respectively (p&lt;0.01). Mean number of abnormal sectors for patients with no stenoses, 1-vessel, and multi-vessel disease were 1.6, 2.5, and 6.3; respectively (p&lt;0.05). The sensitivity and specificity of TPR for detecting a stenosis ≥50% severity was 62% and 86% compared with 62% and 71% for SPECT (NS). When defining territorial ischemia as a SPECT perfusion abnormality plus a stenosis ≥50%, the sensitivity, specificity, positive and negative predictive values were 75%, 95%, 75%, and 95% for combined CTA/CTP imaging, respectively. Conclusions: The transmural perfusion ratio measured from 256x0.5mm MDCT perfusion images can detect the presence of obstructive atherosclerosis with similar accuracy compared with SPECT imaging. The combination of 256x0.5mm MDCT angiography and perfusion imaging may avoid the high false positive rate seen with SPECT imaging alone as well as improve its prediction of territorial ischemia.
P4-17-06: Prognostic Role of Triple Negative Subtype in Breast Cancer Patients with Brain Metastases.
Authors: A Mathew, IE Mathew, MQ Rosenzweig, AM Brufsky
Journal: Cancer Research (2011)

Abstract Background Metastatic breast cancer (MBC) patients with brain metastases (BM) have a poorer prognosis compared to patients with metastases to sites such as bone or other visceral organs. The role of breast cancer subtypes such as triple negative (TN) status and its relationship with other known prognostic factors have not been well delineated in the context of metastatic disease to the brain. We conducted a retrospective single institution cohort study of MBC patients with BM to evaluate the association between TN subtype and overall survival from the diagnosis of BM. Methods: Baseline demographic and tumor specific data including ER, PR and HER2 status were collected on newly diagnosed MBC patients between January 1998 and December 2009. Overall survival was determined from the date of diagnosis of BM. Survival analyses were performed using the Kaplan-Meier method and Cox proportional-hazards model. Results: Data were available on 186 MBC patients with BM, of whom 156 died during a median follow-up of 10.2 months from the diagnosis of BM; median age was 47.9 years. 91% of patients were Caucasian; 25.3% had triple negative disease. Median survival from the period of diagnosis of BM in patients with triple negative disease was 7 months (Interquartile range, IQR: 3–13) as compared to 11 months (IQR: 5–22) in patients who were HER2−positive or ER/PR-positive. Multivariate analysis found a higher risk of death after BM for TN disease subtype, with a hazard ratio for death of 2.89 (95% confidence interval: 1.89−4.44; p&amp;lt;0.001), when adjusted for variables such as age and stage at initial diagnosis of breast cancer, race, the number of metastatic sites, and the use of metastatic chemotherapy. The administration of metastatic chemotherapy had a significant survival benefit in the analyses, with a hazard ratio for death of 0.52 (95% CI: 0.27−0.99; p=0.048). Conclusion: This retrospective cohort study in MBC patients with BM provides evidence for a greater risk of death in those with TN disease as compared to HER2−positive or ER/PR-positive subtypes even after adjusting for other prognostic factors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-06.
Abstract P3-08-04: Impact of CYP3A variation on estrone levels and breast cancer risk
Authors: GM Ross, N Johnson, N Orr, K Walker, L Gibson, E Folkerd, B Haynes, C Palles, B Coupland, M Shoemaker, M Jones, P Broderick, E Sawyer, M Kerin, I Tomlinson, M Zvelebil, S Chilcott-Burns, K Tomczyk, G Simpson, J Willianson, S Hillier, R Houlston, A Swerdlow, A Ashworth, M Dowsett, J Peto, I dos Santos, O Fletcher
Journal: Cancer Research (2012)

Abstract Background: Epidemiological studies provide strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that were associated with premenopausal hormone levels and breast cancer risk. Methods: We measured urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PG) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle, plasma sex hormone-binding globulin (SHBG) and androgenic precursors in up to 763 healthy premenopausal women. We genotyped 642 single nucleotide polymorphisms (SNPs) in these women; a single SNP was further tested for association with breast cancer risk in data from 10,551 breast cancer case patients and 17,535 control subjects. All statistical tests were two-sided. Results: rs10273424 mapping approximately 50kb centromeric to the cytochrome P450 3A (CYP3A) cluster (7q22.1) was associated with a 21.8% reduction in E1G levels (P = 2.7 × 10−9) and a modest reduction in breast cancer risk in cases diagnosed at or before age 50 (OR = 0.91; P = 0.03) but not older cases (odds ratio (OR) = 1.01; P = 0.82). A rare non-synonymous SHBG SNP was associated with reduced plasma SHBG levels. Conclusions: Genetic variation in non-coding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and breast cancer risk in younger cases. Since CYP3A4, the most predominantly expressed CYP3A gene, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents such as tamoxifen, used in the treatment of breast cancer this association may have wider implications. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-04.
P32 * INCREASED PERCENTAGE RESECTION OF TUMOUR VOLUME USING NEURONAVIGATIONAL 3D INTRAOPERATIVE ULTRASOUND: A SINGLE UNIT EXPERIENCE
Authors: B. Vaqas, K. O'Neill, M. Awad
Journal: Neuro-Oncology (2014)

INTRODUCTION: The use of intraoperative 3D navigational ultrasound (Sonowand) offers a relatively inexpensive method of obtaining imaging of intrinsic brain tumours during resection which takes in account brain shift during surgery and also allows better visualisation of the tumour margin to help control resection. We designed a study to measure the volume of tumour resection in 25 consecutive Sonowand cases compared to 25 matched non-ultrasound guided controls. METHOD: A retrospective consecutive case series of 50 patients who underwent resection of an intrinsic tumour was collected, comprising 25 cases using neuronavigational intraoperative 3D ultrasound and 25 with standard neuronavigation without intraoperative ultrasound. The volume of the tumour was calculated both pre- and post-operatively using volumetric analysis software based on T1 contrast sequences from MRI scans. The mean percentage resection of the Sonowand group was compared to that of the control. RESULTS: The percentage resection in the Sonowand group was significantly greater (p < 0.0005) than the control group. The Sonowand group had a percentage resection of 97.7% (95% CI 96.9%- 98.5%) and the non-Sonowand group had a percentage resection of 93.5% (95% CI of 92.1%-94.9%). There was no significant difference in the pre-op volume or tumour location between the two groups. CONCLUSION: The experience in our unit is that Sonowand guided resection results in a greater volume of tumour resection when compared to cases in which intraoperative ultrasound guidance was not used. Further studies are required to show if this results in reduced recurrence and improved survival in patients with intrinsic brain tumours.
Diagnosis of Mantle-Cell Lymphoma Relapse by 18F-FDG PET/CT After Water Gastric Distention
Authors: Ignacio Banzo, Isabel Martínez-Rodríguez, Remedios Quirce, Julio Jiménez-Bonilla, José Manuel Carril
Journal: Clinical Nuclear Medicine (2014)

Proper gastric distention with oral contrast agents is a well-recognized CT technique for imaging of the stomach. We present the basal and after water ingestion F-FDG PET/CT images that show abnormal focal FDG uptake in a clinically unsuspected gastric relapse of mantle-cell lymphoma. The patient had achieved complete remission after chemoradiotherapy and autologous stem-cell transplantation 3 years before. The images obtained after the distention of the stomach with water were crucial to confirm the presence of an FDG-avid lesion in the antrum and to distinguish between physiological and pathological radiotracer uptake. Histological analysis confirmed mantle-cell lymphoma infiltration.