tbuckley/cabot-search huggingface dataset:
OC-156 Analysis of colorectal polyps detected in the English NHS bowel cancer screening programme with emphasis on advanced adenoma and polyp cancer detected: Abstract OC-156 Table 1
Authors: D Majumdar, J Patnick, C Nickerson, M D Rutter
Journal: Gut (2012)

<h3>Introduction</h3> Colorectal cancer is the second most common cause of cancer related death in the UK causing around 16 000 deaths each year. Colorectal adenomas are slow growing precursor lesions which progress to cancer. The lesion of most interest in this context is advanced adenoma (size 10+ mm/with 20%–25% villous histology/high grade dysplasia) as they are of higher risk of progression (2). This study analysed adenomatous lesions detected in NHS BCSP programme. <h3>Methods</h3> Data on each patient entering the NHS BCSP programme is prospectively recorded on the national BCSP database. The database was interrogated for all polyps/adenomas found during the period September 2006 to September 2011. The data were analysed with particular focus on detection of advanced adenoma and polyp cancers. <h3>Results</h3> A total of 65 535 polyps were found, of which 43 954 (67.06%) were confirmed histologically as adenomas. 15 261 advanced adenomas were detected. These accounts for 34.7% of lesions removed and 23.9% of all lesions detected during screening. 842 polyp cancers were found and removed. 1.9% of the adenomatous lesions removed were polyp cancer. The incidence of villous morphology, HGD and polyp cancer, categorised by adenoma size, are shown in the Abstract OC-156 table 1. The presence of villous histology and high grade dysplasia increases with increasing size of adenoma, whereas villous histology begins to plateau for adenomas over 15 mm in size, the incidence of HGD appears linear up to and beyond adenomas of 45mm in size. <h3>Conclusion</h3> 67.06% of all lesions found were histologically confirmed colorectal adenomas. One third of adenomas were advanced adenomas. There is a trend of increase of incidence of cancer and features of advanced neoplasia in adenomas with increasing size. The incidence of AA feature present in lesions below 10mm in size was 10.07%. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Office of National Statistics</b>. UK, 2010. 2. <b>Atkin W</b>, Marson B, Cuzick J. Long term risk of colorectal cancer after excision of ectosigmoid adenomas. <i>N Engl J Med</i> 1992;<b>326</b>:658–62.
Abstract 1800: Targeted therapy using saracatinib adjunctive to castration inhibits progression to castration-resistant prostate cancer in a murine model
Authors: Joy C. Yang, Brian Hu, Blythe Durbin-Johnson, Allen C. Gao, Hsing-Jien Kung, Christopher P. Evans
Journal: Cancer Research (2012)

Abstract Introduction: Prostate cancer treatment with androgen deprivation is typically efficacious for two years prior to the development of castration resistant disease (CRPC). The Src family kinases (SFK) are upregulated with androgen deprivation and have been implicated in the progression to CRPC. Saracatinib is a specific SFK inhibitor that inhibits castration resistant growth and metastases in an animal model using LNCaP cells overexpressing the neuropeptide gastrin-releasing peptide. We test the hypothesis that saracatinib given immediately after androgen deprivation inhibits castration resistant tumor recurrence using a CWR22 xenograft model. Materials and Methods: CWR22 prostate cancer xenografts were injected subcutaneously into nude mice primed with testosterone pellets (21-day release). Twenty-six mice were castrated after adequate tumor development (day 0). Mice in the treatment arm were administered saracatinib from day 7 to day 150. Mice were sacrificed at days 0, 3, 30 and 150. Tumors and sera were collected for analysis including tumor weight, serum testosterone, serum PSA and gene-profile studies. The data was analyzed using the t-test and analysis of variance. Results: CRPC recurrence was significantly inhibited with the administration of saracatinib. The mean weight of tumor recurrence was 0.18 grams with saracatinib compared to 3.20 grams in the control group (p=0.015). Saracatinib was associated with a reduction in serum PSA (1.6 versus 14.7 ng/dl) and testosterone (21.1 versus 24.1 pg/ml) compared to controls, though statistical significance was not reached (p=0.08 and p=0.63, respectively). Gene expression of signaling kinases and their downstream olecules including Src, Etk, FAK, JAK, Stat3, c-myc, β-catenin, NF-κB, Akt, and mTOR is being compared between time points. Conclusions: Saracatinib significantly inhibits castration resistant tumor recurrence when started with androgen deprivation. Additional investigation into the genetic and molecular changes induced by saracatinib with gene microarray and polymerase chain reaction is ongoing. Saracatinib may have a role in combination with androgen deprivation to delay the onset of castration resistant disease. 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 1800. doi:1538-7445.AM2012-1800
Patterns of Efficacy, Toxicity and Treatment Discontinuation in HCC Patients Receiving Capecitabine Monotherapy
Authors: O.M. Abdel-Rahman, M.M. Abdelwahab, M.K. Shaker, S.A. Abdelwahab, M.M. Elbassiony, M.M. Ellithy
Journal: Annals of Oncology (2013)
THU0457 Clinical Courses and Predictors of Outcome in Patients with Monoarthritis
Authors: E.-J. Park, H. Jeong, J. Hwang, J. Lee, J. K. Ahn, H.-S. Cha, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The clinical courses of monoarthritis are diverse, and predictors of the outcome of monoarthritis remain unknown. <h3>Objectives</h3> To evaluate the clinical features and outcomes in patients with monoarthritis and to investigate predictive factors of clinical outcomes. <h3>Methods</h3> A retrospective analysis of 171 patients of chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011 was performed. Baseline characteristics, radiographic findings and the clinical course were reviewed. <h3>Results</h3> Mean age was 42.8 years and 92 (53.8%) were female. Median follow-up duration was 21 months. Most commonly involved joints were knees (24.0%) followed by wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Of these, 31 (18.1%) patients were diagnosed with rheumatoid arthritis (RA), 23 (13.5%) patients with peripheral spondyloarthritis (SpA), and 19 (11.1%) patients with Behcet`s disease (BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained undiagnosed monoarthritis with relatively shorter symptom duration and required less treatment. The initially involved joint was a predictive factor for the final diagnosis; the wrist joint for RA (OR 11.58, 95% CI 4.80 to 29.93, p &lt; 0.001), the ankle joint for SpA (OR 6.19, 95% CI 2.38 to 16.08, p &lt; 0.001), and the knee joint for BD (OR 3.43, 95% CI 1.29 to 9.15, p = 0.014). The bony erosion at baseline was associated with progression to oligo- or polyarthritis (OR 2.88, p = 0.030) and with radiographic progression. <h3>Conclusions</h3> In patients presenting with monoarthritis, final diagnosis is established in less than half of patients, and majority of undiagnosed patients show benign clinical course. The initially involved joint, presence of erosion at baseline are predictors for the final diagnosis and clinical outcomes. <h3>References</h3> Binard A, Alassane S, Devauchelle-Pensec V, Berthelot JM, Jousse-Joulin S, Chales G, et al. Outcome of early monoarthritis: a followup study. J Rheumatol 2007;34:2351-7. Inaoui R, Bertin P, Preux PM, Treves R. Outcome of patients with undifferentiated chronic monoarthritis: retrospective study of 46 cases. Joint Bone Spine 2004;71:209-13. Rasmussen G, Reimann I, Andersen RB. Monoarthritis, clinical and histological examination. Scand J Rheumatol 1973;2:65-9. Blocka KL, Sibley JT. Undiagnosed chronic monarthritis. Clinical and evolutionary profile. Arthritis Rheum 1987;30:1357-61. Kaarela K, Tiitinen S, Luukkainen R. Long-term prognosis of monoarthritis. A follow-up study. Scand J Rheumatol 1983;12:374-6. <h3>Disclosure of Interest</h3> None Declared
PD01-08: Heterogeneity of Lapatinib Responses in HCC1954 HER2−Overexpressing Breast Cancer Cells Revealed by Single-Cell Automated Microscopy.
Authors: KN Hardeman, D Tyson, V Quaranta
Journal: Cancer Research (2011)

Abstract In breast cancer, 20–30% of patients present with HER2 overexpression, making them potential candidates for targeted HER2 therapies such as lapatinib. Lapatinib is a dual, intracellular tyrosine kinase inhibitor of HER2 &amp; EGFR and is standard care for metastatic breast cancer. Drug resistance to this type of therapy is a major cause of death in cancer patients. Intra-tumor heterogeneity with respect to drug response can be a driving force for relapse and/or drug resistance. In current drug response end-point assays (IC50), information on heterogeneity is lost because cell differences are averaged out over the whole population. To produce a more realistic appreciation of drug response variability within a tumor, our lab has developed an extension of high content automated microscopy, called Extended Time Resolved Automated Microscopy (ETRAM). ETRAM entails the visual tracking of single cells with fine temporal &amp; spatial resolution, allowing for the calculation of proliferation, death, and quiescence rates from image stacks and movies. HER2+ breast cancer HCC1954 cells were fluorescently labeled w/a nuclear tag (H2BmRFP) and treated w/lapatinib in a dose-dependent manner, from 2000 nM to 0 nM (DMSO control). Using the ETRAM method we followed nearly 1000 single cells/treatment condition over 72 hours, acquiring images every 10–12 minutes. Unexpectedly, we discovered that small but significant subpopulations of HCC1954 cells are unaffected by high lapatinib concentrations (2000 nM) and continue to divide. Furthermore, a substantial subpopulation responds to high lapatinib by entering quiescence, not apoptosis. Since HCC1954 cells have a previously reported lapatinib IC50 of 300 nM, our data demonstrate a need to further investigate these subpopulations of cells in order to determine their contribution to the IC50. Image stacks are being further analyzed to extract cellular metrics of division, quiescence and death rates in the presence of lapatinib. We are also investigating single cells by immunofluorescence of signaling molecules in the HER2 pathway, along with downstream targets such as PI3K, mTOR/AKT, SHC, and RAF1, to assess molecular differences regarding dividing and quiescent subpopulations in lapatinib, versus lapatinib-sensitive cells that apoptose. Our ETRAM-based single cell analyses may stimulate a re-interpretation of lapatinib responses in HER2−overexpressing breast cancer, and hopefully point to improved strategies of lapatinib treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD01-08.
SP0035 Rheumatology Training in Europe: An Overview
Authors: F. Sivera
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Rheumatology specialty training is the period in which trainees lay the foundation of their knowledge, skills and professional behavior essential to a high quality practice as rheumatologists. This training has a direct impact on the standards of care conferred to patients with rheumatic musculoskeletal diseases (RMDs). The definitions of the aims, content and structure of the specialty training remain within the exclusive domain of national authorities. However, the free circulation of medical specialists within the European Union has led to an increase in the percentage of rheumatologists who practice in a different country from the one they trained. An increased degree of harmonization is deemed important to guarantee the standards of care for patients with RMDs. The European Board of Rheumatology - a Section of UEMS has provided a reference framework of core competences to be achieved by the end of rheumatology specialty training. Even though almost all European national authorities have endorsed this curriculum framework, each country has retained full autonomy to decide to what extent they are brought into practice. In this presentation, a review of the existing data comparing rheumatology training across European countries will be performed. Also, the experience of other specialties in assessing the differences in national curricula and providing instruments to facilitate a greater degree of cross-country harmonization will be presented. <h3>Disclosure of Interest</h3> None Declared
Abstract P3-02-09: Cost-effectiveness of screening with additional MRI for women with familial risk for breast cancer without a genetic predisposition
Authors: S Saadatmand, EA Heijnsdijk, EJ Rutgers, N Hoogerbrugge, JC Oosterwijk, RA Tollenaar, M Hooning, I-M Obdeijn, HJ de Koning, MM Tilanus-Linthorst
Journal: Cancer Research (2012)

Abstract Background: To reduce mortality risk, women with a family history of breast cancer are often screened with mammography before 50 years of age. Additional Magnetic Resonance Imaging (MRI) can improve sensitivity. MRI screening is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history of breast cancer without a proven mutation cost-effectiveness is not clear. We evaluated the cost-effectiveness of additional MRI for women with a familial risk in the largest prospective MRI screening study: the Dutch MRI Screening Study (MRISC). Materials &amp; Methods: Between 1999 and 2007 a total of 1597 women (8370 women years at risk) between 25–70 years, with an estimated cumulative lifetime risk of 15–50% for breast cancer participated in the MRISC. Women were screened with clinical breast examination (CBE) every six months and annual mammography and MRI. We calculated the costs per detected breast cancer. In addition, MRISC data were incorporated into a micro simulation screening analysis model: MISCAN. This model simulates screening programs with different screening modalities and time intervals. Different screening schemes were evaluated and the cost per life-year gained (CLYG) estimated. Results: Forty-seven breast cancers, including 9 Ductal Carcinoma in Situ, were detected. Screening with additional MRI leads to a cost per detected breast cancer treated of €101,962. In increasing age-cohorts the cost decreased, probably due to the higher breast cancer incidence. The cost per detected and treated breast cancer in age group 40–50 years doubled in the age group &amp;gt;60 years. We will demonstrate these results more extensively. With MISCAN modeling we predicted that screening with this scheme from age 35 to 60 years reduces breast cancer mortality by 30% at a CLYG of €119,945 (3.5% discounting), compared to 21% estimated mortality reduction at €45,707 CLYG with mammography and CBE alone. Conclusion: Screening with MRI may improve survival for women with familial risk for breast cancer, but is expensive. However, it may be cost-effective for a select group. We will discuss subgroups that may benefit from MRI screening and in which age category MRI was most effective in our study. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-09.
P07 * ARE ALL PATIENTS WITH SUSPECTED BRAIN TUMOUR ON CRANIAL IMAGING REFERRED PROMPTLY FOR MDT DISCUSSION?
Authors: C. Barnes, A. Varma, P. Kane
Journal: Neuro-Oncology (2014)

INTRODUCTION: The IOG for Brain and CNS tumours advises that all new cases of suspected CNS tumour should be referred to the Brain & CNS tumours MDT for discussion within a strict timescale. We audited new tumour referrals to MDT using the following standards: (1) All newly diagnosed/ suspected brain tumours are logged to the MDT database; (2) Logging to the database should be done within 7 days of image reporting. METHOD: A retrospective study of all radiology reports of CT/MRI head scans performed in two hospital Trusts in a 4 week period. Scans were identified from the PACS system of each Trust and each scan report was manually reviewed for a suspected new diagnosis of brain tumour. All positive scans were correlated with the MDT database. RESULTS: All radiology reports for CT/MRI head scans performed in the period 30/09/13-27/10/13 were assessed. 2125 scans were identified and, of these, 42 were reported as showing possible/definite new diagnosis of brain tumour. (22 male, 20 female, mean age 62.5). Only 48% (n = 20) of cases were subsequently referred and logged to the MDT database, with 50% (n = 10) logged within 7 days. All high grade primary brain tumours (n = 6) were referred to MDT. Of the non-referred cases, the most common diagnosis was cerebral metastasis (59%). Review of non referred cases indicated that reasons for non-referral included: (1) Clinical judgement conflicted with guidelines; (2) Patient died; (3) Re-scan excluded tumour diagnosis. Common reasons for delayed referral were: (1) Physician awaited a re-scan; (2) Benign tumour diagnosis. CONCLUSION: Improvement of the awareness regarding the criteria for referral to Brain tumour MDT is needed, especially in metastatic and non-high grade Tumours.
Targeting CD30 as therapy for Hodgkin’s disease. Phase II results with the monoclonal antibody SGN-30
Authors: J. P. Leonard, A. Younes, J. D. Rosenblatt, A. Gopal, L. C. Pinter-Brown, N. L. Bartlett, L. J. Burns, A. Forero, J. Barton
Journal: Journal of Clinical Oncology (2005)

2553 Background: The CD30 antigen is expressed on tumor cells from patients with Hodgkin’s Disease (HD) and other hematologic malignancies. Phase I results with SGN-30, a chimeric anti-CD30 monoclonal antibody, have demonstrated that the drug is well tolerated and shows signs of anti tumor activity with both disease stabilization and objective tumor response in patients with HD and non-Hodgkin’s lymphoma (NHL). Methods: Patients with confirmed CD30+ relapsed or refractory HD were enrolled into a multi-center study of SGN-30 administered initially at a dose of 6 mg/kg once per week for 6 doses. The dose was escalated to 12 mg/kg after evaluation of the first 15 patients. Results: Patient characteristics: Dose cohort 6 mg/kg (15 pts), 12 mg/kg (7 pts to date). Median age 34 years. Median number of prior therapies 3. All patients had received prior ABVD chemotherapy, 73% had previous stem cell transplant. Efficacy: 6 mg/kg: 6 patients had stable disease with mean duration of 4.8 months (range 2–8 months). 9 patients had progressive disease. On the basis of these results the dose was escalated to 12 mg/kg. At this dose level,7 patients have accrued to date, with one evaluable for response (progressive disease). Tolerability: With the exception of 1 patient with grade 3/4 neutropenia treated at 6 mg/kg there have been no grade 3/4 laboratory adverse events. The most common adverse event at the 6 mg/kg dose was fatigue occurring in 6 patients. Anorexia, chest pain, diarrhea, pruritus, rash and wheezing were seen in 10% or more patients at this dose level. At the 12 mg/kg dose, headache, rash and nausea have been seen in 2 or more subjects. Conclusions: SGN-30 is well tolerated at both 6 and 12 mg/kg/week x 6, with efficacy and correlative analyses ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seattle Genetics Seattle Genetics
Abstract SY39-01: Harnessing cancer genome diversity for intervention target discovery and development
Authors: Michael A. White
Journal: Cancer Research (2012)

Abstract The diverse assortment of somatic lesions associated with human cancer initiation and progression presents a formidable challenge against efforts to develop molecularly targeted therapeutic interventions. Here we are modeling genetic diversity within lung cancer using a panel of over 100 non small cell lung cancer derived cell lines. Broad-scale parallel testing of genetic and chemical perturbations, together with high-resolution genomic characterization, is being used to parse this panel into subtypes with shared target opportunities and molecular correlates that predict response to target intervention. In this way, we have begun to identify somatic allele combinations that drive sensitivity to selective gene depletions and to synthetic small molecules that target these genes and/or the biological processes they serve. 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 SY39-01. doi:1538-7445.AM2012-SY39-01
P04.14 * IDH1 MUTATION IN LOW-GRADE GLIOMAS RELATED TO EPILEPSY AS INITIAL SYMPTOM
Authors: A. Duran-Pena, K. Mokhtari, Y. Marie, A. Alentorn, J. Delattre, A. Idbaih, M. Sanson, C. Vecht
Journal: Neuro-Oncology (2014)

Seizures are common in low-grade gliomas (LGGs) and are highly correlated with the presence of the isocitrate-dehydrogenase 1 mutation (IDH1m). We aimed to explore the correlation between the IDH1m in LGGs and the presence of epilepsy as initial symptom. METHODS: Observational retrospective study on 164 patients with LGGs (86 oligodendrogliomas, 41 astro-oligodendroglial tumors and 37 astrocytomas) of whom 71% had seizures as initial symptom, analyzed according to Fisher's exact and Mann Whitney test. RESULTS. There was no difference in age or brain tumor location in patient with or without seizures. Seizures were more frequent in the group of IDH1m (92/117; 78 %) vs. (27/47; 57.4%), p = 0.01. Fronto-insular location was more frequent in the group of IDH1m (75/117; 65%) vs (13/47; 27%), p = 0.01. There was no difference if analyzed by histological type of low-grade gliomas, except for oligodendrogliomas, in which seizures were more frequent with IDH1m 52/65 (80,0 %) p = 0.02. The average age of the IDH1m with seizures was not significantly higher: 41.5 yrs vs. 39.5 yrs without seizures, p = 0.27. The type of seizures simple/complex partial (64/117; 55%) vs. generalized (53/117; 45%) is similar regardless of the presence of IDH1m, p = 0.8 CONCLUSION. Epilepsy as initial symptom in oligodendrogliomas is associated with the presence of IDH1 mutation. Fronto-insular location is more frequent among IDH1 mutated LGGs. There is no difference in type of seizures among IDH1 mutated LGGs.
516 RANDOMIZED CONTROLLED TRIAL OF PROPHYLACTIC ENTECAVIR IN HBSAG-NEGATIVE/ANTI-HBC-POSITIVE LYMPHOMA PATIENTS UNDERGOING RITUXIMAB-BASED CHEMOTHERAPY: PRELIMINARY REPORT
Authors: Y.-H. Huang, Y.-C. Hong, L.-T. Hsiao, T.-J. Chiou, C.-H. Tzeng, H.-C. Lin, S.-D. Lee
Journal: Journal of Hepatology (2012)
How do forward models work? And why would you want them?
Authors: Jeffrey Bowers
Journal: Behavioral and Brain Sciences (2013)

Abstract The project of coordinating perception, comprehension, and motor control is an exciting one, but I found it hard to follow some of Pickering &amp; Garrod's (P&amp;G's) arguments as presented. Consequently, my comment is not so much a disagreement with P&amp;G but a query about the logic of forward models: It is not clear how they are supposed to work, nor why they are needed in this (or many other) contexts, and toward that end I present an alternative idea.