tbuckley/cabot-search huggingface dataset:
OC-076 Extension of the Bowel Cancer Screening Programme to those aged 70–74 years, Torbay's experience: Abstract OC-076
Authors: M A Feeney, L Beard, K Bird, D C Williams, R D Pullan
Journal: Gut (2010)

<h3>Introduction</h3> The Bowel Cancer Screening Programme (BCSP) was launched in July 2006 to screen those aged 60–69 years. In September 2006 the South Devon Screening centre started screening and in September 2008 it was one of five sites to extend screening to those aged 70–74 years. This age group was not included in the pilot studies. This study has been undertaken to assess the uptake of the investigations in the over 70 s in the Torbay area (population 270 000). <h3>Methods</h3> The data were collated by analysing central records of test kits sent out from our hub at Guildford and also our local prospective data set for all patients with positive faecal occult blood tests (FOBt). The first year of screening for each age group was analysed and compared, that is, for the 60–69 year old group, the data studied relate to the period 9/9/06 to 30/10/07. For the older age group (70–74 years) the study period was 9/9/08 to 30/10/09. Most subjects take a couple of weeks to return the kits so the study period was extended to allow for 12 months of colonoscopy data to be analysed. <h3>Results</h3> In those over 70 years (compared to those 60–69 years) There is a very high rate of return of the FOBt kits (70% vs 59%) The FOBt +ve rate was much higher in this age (2% vs 1.1%) There was a lower rate of DNA at the nurse led clinic (0% vs 2%) Higher rate of informed dissent (ie, no further investigation chosen by the patient) (12% vs 2%) Slightly more patients were unfit for colonoscopy (2% vs 0.6%) There was a lower rate of colonoscopy (83% vs 92%) Colonoscopy completion rate was very similar (98.8% vs 99.3%) Colonoscopy findings in those over 70: Cancer rate 11% and polyp detection rate 34.5% which are in line with the incidence rates seen within the BCSP. Normal colonoscopies were recorded in 29%. <h3>Conclusion</h3> In our population the rate uptake of the BCSP (returning FOBt) was higher in those over 70 years and they were twice as likely to have positive FOBt as the younger age group. Most of this older group was fit for colonoscopy and there was a significant yield of cancer and polyps. This study will help other screening centres to estimate the number of additional colonoscopies required to provide bowel screening for the extended age group up to 75 years. Bowel screening will be rolled out nationally to this age group during 2010.1
Pembrolizumab for patients with advanced prostate adenocarcinoma: Preliminary results from the KEYNOTE-028 study
Authors: A. Hansen, C. Massard, P.A. Ott, N. Haas, J. Lopez, S. Ejadi, J. Wallmark, B. Keam, J.-P. Delord, R. Aggarwal, M. Gould, P. Qiu, S. Saraf, S. Keefe, S.A. Piha-Paul
Journal: Annals of Oncology (2016)
Phase I Study of Triapine® and Cytarabine (ara-C) in Patients with Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndrome (MDS).
Authors: Karen W.L. Yee, Jorge Cortes, Guillermo Garcia-Manero, Srdan Verstovsek, Alessandra Ferrajoli, William G. Wierda, Deborah Thomas, Stefan Faderl, Ivan King, Susan M. O’Brien, Mario Sznol, Francis J. Giles
Journal: Blood (2005)
PTH-103 Audit of screening for coeliac disease in iron deficiency anaemia
Authors: C McArthur, P S Phull
Journal: Gut (2010)

<h3>Introduction</h3> The BSG guideline for the management of iron-deficiency anaemia (IDA) recommends that all patients should be screened for coeliac disease by coeliac serology. If serology is negative, small bowel biopsies (SBB) are not required at upper GI endoscopy (UGIE), unless other features are present suggesting the diagnosis of coeliac disease. If coeliac serology is positive, coeliac disease should be confirmed by SBB. Previous studies had demonstrated poor compliance with this recommendation.1 The aim of this audit was to assess the number of patients undergoing UGIE for investigation of IDA who were screened for coeliac disease. <h3>Methods</h3> Retrospective audit of all patients undergoing UGIE at our institution between January 2007 and May 2008. Patients were identified from the endoscopy database (Unisoft), and coeliac serology and duodenal biopsy results were retrieved from the pathology results system. IDA was defined as Ferritin &lt;12 μg/dl and/or Hb &lt;13.5 in men and &lt;12 in women with MCV &lt;82. <h3>Results</h3> During the 15-month period of the audit, a total of 5376 UGIEs were performed. Of these, “anaemia” was recorded as the indication in 825 cases; however, only 424 (7.9%) had confirmed IDA. Of these 424 patients, 122 (28.8%) had anti-endomysial antibodies checked prior to UGIE; positive antibodies were present in 10 (8.2%) of these patients. SBB was performed in 202 (47.6%) of the 424 patients: 10 patients with positive antibodies (confirmed coeliac disease in 7, equivocal results in 2 and normal histology in 1 patient), 121 with no previous serology test (1 confirmed coeliac disease, 2 equivocal histology), and 71 with negative antibodies (2 confirmed coeliac disease, 1 equivocal histology). Overall, 243 (57.3%) of the 424 patients with IDA were screened for coeliac disease by either serology or SBB. The diagnosis was confirmed in 10 patients (2.4%), with equivocal histology in a further five patients (1.2%). <h3>Conclusion</h3> The results of this audit demonstrate poor compliance with the BSG guideline for coeliac disease screening in IDA.
OP20DRUGGABLE PROGNOSTIC MARKERS IN PAEDIATRIC EPENDYMOMA; IS BLBP THE SOLUTION?
Authors: D. Sabnis, L.C.D. Storer, L. Simmonds, S. Blackburn, J.-P. Kilday, J. Lowe, G.R. Grundy, I. Kerr, B. Coyle
Journal: Neuro-Oncology (2015)

INTRODUCTION: Paediatric ependymomas are aggressive treatment resistant tumours with a tendency to relapse. This behaviour is consistent with an underlying sub-population of therapy resistant cancer stem cells. Blbp (brain lipid binding protein) is a marker for radial glial cells, the proposed stem cells of origin in ependymoma. PPARs (peroxisome proliferator activated receptors) are transcription factors; two of which (γ and δ) play a key role in modulating the transcriptional activity of Blbp. METHOD: Blbp immunohistochemistry (IHC) staining was performed on patient samples obtained from two trial cohorts; a chemotherapy-led infant trial (CNS 9204) and a radiotherapy-led trial (CNS 9904). Blbp expression in cell lines and stem cell enriched neurospheres was performed using RT-PCR. Viability assays were carried out to assess proliferation and potentiation of response to chemotherapy in 2D & 3D cultures. Cell migration and invasion were assessed by scratch assays and 3-D migration assays respectively. RESULTS: Blbp expression correlated with reduced overall survival (OS) in both trials (CNS9204- 5yr OS 45% vs 80%, P = 0.011 and CNS9904- 5yr OS 38% vs 85%, P = 0.002). 5/5 ependymoma cell lines expressed Blbp which was elevated in stem cell enriched neurospheres. Treatment with three PPAR antagonists diminished Blbp expression and proliferation in 2D and 3D cultures. Cell migration and invasion were also diminished. CONCLUSION: These findings constitute the first conclusive evidence that Blbp is an independent predictor of poor survival in paediatric ependymomas. In addition, treatment with PPAR antagonists may represent an effective novel therapy to prevent invasion in paediatric ependymoma patients.
Second Line Therapy with Second Generation TKI After Intolerance to Imatinib Based Treatments Showed High Overall Survival in Contrast to Second Line Therapy After Resistance; Results of the Randomized CML Study IV
Authors: Susanne Saussele, Michael Lauseker, Ulrike Proetel, Martin C. Müller, Benjamin Hanfstein, Annette Schreiber, Florian Nolte, Gabriela M. Baerlocher, Gerhard Ehninger, Dominik Heim, Dieter K. Hossfeld, Stefan W. Krause, Christoph Nerl, Hans Pralle, Joerg E. A. Schubert, Hermann Einsele, Matthias Hänel, Anthony D. Ho, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Wolf Karsten Hofmann, Jörg Hasford, Markus Pfirrmann, Andreas Hochhaus, Rüdiger Hehlmann
Journal: Blood (2011)
Abstract 388: EGR1 is a mediator of TWEAK-Fn14 pathway induced prostate cancer bone metastasis
Authors: Amir H. Ameri, JuanJuan Ivy Yin, Keith Jansen, Simeng Wang, Jessica Snyder, Paul Hynes, Kathleen Kelly
Journal: Cancer Research (2015)

Abstract Patients with advanced or castration-resistant prostate cancer have a high probability of developing bone metastasis. However, the molecular mechanisms driving bone metastasis in prostate cancer remain poorly understood. We have previously demonstrated that Fn14 expression is increased significantly in metastatic lesions from prostate cancer patients. Fn14 is a member of the TNF receptor family, and our in vivo study using DU145/RasB1 cells indicated that the TWEAK-Fn14 pathway promotes prostate cancer bone metastasis via the canonical NFκB pathway. However, the downstream targets of the TWEAK-Fn14 pathway have yet to be characterized in prostate cancer cells. To elucidate the precise mechanism underlying Fn14-promoted metastasis, we analyzed the gene expression profile of highly metastatic DU145/RasB1 and low metastatic DU145/RasB1 Fn14depleted (Fn14KD) cells. Fn14 depletion significantly altered expression of 147 genes, including ECM components, cell adhesives, and cytoskeletal regulators. In addition, DU145/RasB1 and DU145/RasB1 Fn14KD cells responded differently to TWEAK treatment. We found increased expression of early growth response 1, (EGR1), in the TWEAK-treated DU145/RasB1 cells relative to DU145/RasB1 Fn14KD cells. To determine if EGR1 plays a role in prostate cancer metastasis, we depleted EGR1 expression with two shRNAs in highly metastatic DU145/RasB1 cells. Our results show that both EGR1 shRNAs significantly inhibited bone metastasis in vivo. We also found that EGR1 expression was decreased when the NFκB pathways were inhibited by an IκB super repressor in DU145/RasB1 cells. Interestingly, both Fn14 depletion and EGR1 depletion increased TFPI2 expression and inhibited adhesion to fibrin. Fibrin has been shown to facilitate metastatic spread by assisting platelet adhesion to circulating tumor cells. These results suggest one scenario whereby activation of Fn14 signaling may promote prostate cancer bone metastasis through enhancing tumor-platelet interaction via an EGR1-dependent mechanism. Citation Format: Amir H. Ameri, JuanJuan Ivy Yin, Keith Jansen, Simeng Wang, Jessica Snyder, Paul Hynes, Kathleen Kelly. EGR1 is a mediator of TWEAK-Fn14 pathway induced prostate cancer bone metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 388. doi:10.1158/1538-7445.AM2015-388
Sustained NF-Kappa B Activity In Chronic Lymphocytic Leukemia Is Independent of Genetic and Epigenetic Modifications of the Tumor Suppressor Genes CYLD and A20
Authors: Lukas P. Frenzel, Janine Schwamb, Rainer Claus, Julia Claasen, Reinhild Brinker, Christian P. Pallasch, Christoph Plass, Clemens-Martin Wendtner
Journal: Blood (2010)
Premorbid obesity protects against critical illness-induced muscle wasting and weakness
Authors: Chloë Goossens, Mirna Marques, Sarah Derde, Sarah Vander Perre, Thomas Dufour, Steven Thiessen, Fabian Güiza, Thomas Janssens, Greet Hermans, Ilse Vanhorebeek, Katrien De Bock, Greet Van den Berghe, Lies Langouche
Journal: Endocrine Reviews (2016)
Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization
Authors: Sun Hong Yoo, Jeong Won Jang, Jung Hyun Kwon, Seung Min Jung, Bohyun Jang, Jong Young Choi
Journal: Clinical and Molecular Hepatology (2016)

Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE.This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC.Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation.Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.
Age Adjusted Telomere Length Decreases Following Treatment for Pediatric Acute Lymphoblastic Leukemia, but Does Not Predict Toxicity
Authors: Pasquale M Barbaro, Marion Mateos, Luciano Dalla-Pozza, Anthea Ng, Glenn M Marshall, Jodie E Giles, Rosemary Sutton, Rebecca Dagg, Loretta Lau, Hilda A Pickett, Roger R Reddel
Journal: Blood (2015)
The Presence of FLT3/ITD Mutations Is an Independent Prognostic Factor in Acute Myeloid Leukemia Patients with Normal Karyotype.
Authors: Yeo-Kyeoung Kim, Je-Jung Lee, Yu-Ra Lee, Il-Kwon Lee, Hee-Nam Kim, Nan-Young Kim, Kyeong-Soo Park, Deok-Hwan Yang, Moo-Rim Park, Hyeoung-Joon Kim
Journal: Blood (2004)
Pentostatin for First-Line Salvage Therapy of Steroid-Refractory Intestinal Acute Graft-Versus-Host Disease; a Dual Center Retrospective Analysis
Authors: Stefan A. Klein, Thomas Schmitt, Gesine Bug, Thomas Luft, Sabine Mousset, Ute Hegenbart, Wolf-Karsten Hofmann, Anthony D. Ho, Hans Martin, Peter Dreger
Journal: Blood (2010)
Abstract A2-32: Identification of withaferin A as a novel cancer stem cell inhibitor to overcome drug resistance in non-small cell lung carcinoma
Authors: Tai-shan Cheng, Yu-Chen Tsai, Alexander T. H. Wu, Peter M. H. Chang, Wei-Hsiang Hsu, Jin-Mei Lai, Chi-Ying Huang
Journal: Cancer Research (2015)

Abstract Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance. In this study, we focus on screening drugs that target CSCs to improve the current treatment outcome and overcome drug resistance in patients with lung cancer. We used publicly available embryonic stem cell and CSC-associated gene signatures to query the Connectivity Map (CMap) for potential drugs that can, at least in part, reverse the gene expression profile of CSCs. High scores were noted for several phenothiazine-like antipsychotic drugs, including trifluoperazine and perphenazine. The combination of gemcitabine with either trifluoperazine or perphenazine shows synergistic effects in anti-NSCLC cells. By using L1000 and CMap analysis, we identified withaferin A (WA) as a potential drug, which shares similar gene expression patterns to trifluoperazine or perphenazine combine with gemcitabine and to reverse differential gene expression of stem-like cell vs. differential cell. Further experiments demonstrated that WA significantly suppressed cancer stemness associated phenotypes, shown by decreasing side population and tumor spheroid formation. Furthermore, WA was accompanied by down-regulation of JAK2/STAT3 signaling pathway. The combination of WA and cisplatin significantly reduced the number of cancer spheroids and attenuated the proportion of ALDH+ cell population in CL97 lung spheroids, which was resistant to cisplatin treatment alone. In vivo study also demonstrated the anti-tumor effect of WA treatment. In conclusion, WA was identified as a potential anti-cancer stem cell inhibitor, which could also inhibit tumorigenesis and overcome cisplatin resistance in lung cancer. Citation Format: Tai-shan Cheng, Yu-Chen Tsai, Alexander T. H. Wu, Peter M. H. Chang, Wei-Hsiang Hsu, Jin-Mei Lai, Chi-Ying Huang. Identification of withaferin A as a novel cancer stem cell inhibitor to overcome drug resistance in non-small cell lung carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-32.
Abstract 4815: Tumor heterogeneity of advanced primary lung cancer evaluated by multiregion sequencing
Authors: Sang-Won Um, Je-Gun Joung, Su Yeon Lee, Joon Seol Bae, Jinha Park, Woong-Yang Park
Journal: Cancer Research (2015)

Abstract Background: Cancers are composed of cells with distinct genetic and phenotypic characteristics. Tumor heterogeneity in each patient may influence on personalized medicine strategies that depend on results from single tumor-biopsy samples. However, tumor heterogeneity in advanced primary lung cancer has not been well studied. The purpose of this study was to investigate the tumor heterogeneity in advanced primary lung cancer. Methods: We sequenced fourteen regions from four patients who were suspicious for primary lung cancer with multiple lymph node metastasis. Tumor samples were obtained from primary tumor and metastatic lymph node(s) or distant metastasis using bronchoscopic forcep biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, and percutaneous needle biopsy. The profiles of somatic mutations, copy number alterations and gene expression were compared among primary tumor and metastatic sites in each patient. Clonal evolution was evaluated using the concept of cancer cell fraction by SciClone analysis. Results: We performed multiregion whole exome sequencing and RNA sequencing on three non-small cell lung cancers (2 adenocarcinomas [TH1 and TH4] and 1 squamous cell carcinoma [TH2]) and one small cell lung cancer (TH3). EML4-ALK fusion was noticed in TH1 and TH4. There was profound tumor heterogeneity in terms of somatic mutation, copy number alteration, or gene expression in each patient. The frequency of private somatic mutation from spatially distinct regions were 59% in TH1, 44% in TH2, 13% in TH3, and 30% in TH4. Known driver mutation was also heterogeneous in TH1 and TH2. Analysis of the clonal architecture confirmed the presence of clonal heterogeneity in each patient. Phylogenetic reconstruction revealed the evidence of branched clonal evolution. Conclusions: Tumor heterogeneity was noticed from spatially distinct regions from advanced primary lung cancers. The single biopsy specimens may not represent the whole landscape of genetic alteration in advanced primary lung cancers. Citation Format: Sang-Won Um, Je-Gun Joung, Su Yeon Lee, Joon Seol Bae, Jinha Park, Woong-Yang Park. Tumor heterogeneity of advanced primary lung cancer evaluated by multiregion sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4815. doi:10.1158/1538-7445.AM2015-4815
Abstract 2140: Dual Wnt and EGFR-MAPK dependency of <i>BRAFV600E</i>-mutant colorectal cancer
Authors: Youzhen Wang, Michael Palmer, Savina Jaeger, Linda Bagdasarian, Shumei Qiu, Steve Woolfenden, Ronald Meyer, Guizhi Yang, John Green, Shifeng Pan, Jun Liu, Hui Gao, Z. Alexander Cao, Andrea Myers, Margaret E. McLaughlin
Journal: Cancer Research (2015)

Abstract Aberrant Wnt pathway activation due to inactivating mutations in the gene encoding RNF43 (an E3 ubiquitin ligase that promotes degradation of the Wnt receptors Frizzled and LRP6) may contribute to the unresponsiveness of BRAFV600E-mutant colorectal cancer (CRC) to BRAF inhibitors. Analysis of The Cancer Genome Atlas (TCGA) CRC data set reveals a striking co-occurrence of the BRAFV600E mutation and truncating mutations in RNF43. RNF43 mutations are likely to be functionally significant, as RNF43 mutations and mutations in the β-catenin destruction complex component APC are almost completely mutually exclusive. The vast majority of BRAFV600E;RNF43-mutant CRCs are hypermutable [microsatellite instability (MSI)-high phenotype]. The mismatch repair deficiency in these tumors may directly contribute to RNF43 mutagenesis, as RNF43 mutations tend to be small insertions/deletions in homopolymeric tracts. To determine if RNF43 mutations confer Wnt dependency in BRAFV600E-mutant CRC, we treated three BRAFV600E;RNF43-mutant CRC patient-derived xenograft (PDX) models with the porcupine inhibitor WNT974 (formerly LGK974), which blocks the palmitoylation and secretion of Wnt ligands. Single agent WNT974 anti-tumor activity was observed in 2/3 PDX models, and correlated with decreased tumor cell proliferation and mucinous differentiation. Single agent anti-tumor activity with the BRAF inhibitor LGX818 was also observed in 2/3 PDX models. No single agent anti-tumor activity was observed with the EGFR inhibitor cetuximab. The double combinations of WNT974+LGX818 and LGX818+cetuximab, and the triple combination of WNT974+LGX818+cetuximab were efficacious in all three BRAFV600E;RNF43-mutant CRC PDX models. In summary, the Wnt pathway and the EGFR-MAPK pathway may jointly promote tumorigenesis of BRAFV600E-mutant CRC, providing a strong rationale to treat patients with BRAFV600E-mutant CRCs harboring upstream Wnt pathway mutations with combinations of WNT974, LGX818 and/or cetuximab. Citation Format: Youzhen Wang, Michael Palmer, Savina Jaeger, Linda Bagdasarian, Shumei Qiu, Steve Woolfenden, Ronald Meyer, Guizhi Yang, John Green, Shifeng Pan, Jun Liu, Hui Gao, Z. Alexander Cao, Andrea Myers, Margaret E. McLaughlin. Dual Wnt and EGFR-MAPK dependency of BRAFV600E-mutant colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2140. doi:10.1158/1538-7445.AM2015-2140