tbuckley/cabot-search huggingface dataset:
Abstract 3632: Nonclinical pharmacokinetics and safety of Angiocal, the first VEGF-A-specific alternative scaffold protein entering clinical development for cancer
Authors: Hendrik Gille, Jürgen Christian, Martin Hülsmeyer, Todd Meyer, Ali Amirkhosravi, Laurent P. Audoly, Angelika C. Stern, Kristian Jensen, Andreas M. Hohlbaum
Journal: Cancer Research (2011)

Abstract Anticalins are high affinity scaffold proteins based on human lipocalins and represent a new class of biologics. Although lipocalins share limited sequence identity among each other they are all made up of a single conserved beta-barrel. The four loops protruding from the opening of the calyx contribute to the observed various binding functions of different lipocalins. The loop residues of human tear lipocalin were randomized to generate a combinatorial library and successive rounds of panning and screening were employed to generate an Anticalin with high affinity and specificity for VEGF-A, Angiocal. Angiocal was found to antagonize VEGF-A function by preventing its interaction with cognate membrane receptors. Following the initial characterization in cell-based and in vivo models as communicated previously (AACR 2008 #4077, AACR 2009 #2318) we sought to estimate the human pharmacokinetics of Angiocal by interspecies scaling. Therefore, PK profiles in mice, rats and cynomolgus monkeys were obtained and will be presented. Therapeutic antibodies such as bevacizumab are usually well tolerated while significant toxicities occur in a subset of patients, for example leading to an enhanced risk for thromboembolic events. It has been demonstrated that bevacizumab forms multimeric immune complexes in vivo which may be a cause for these effects. Furthermore, immune complex deposition in glomeruli of the kidney may cause glomerulosclerosis. With respect to thromboembolic complications of bevacizumab use, these were mirrored in human FcgammaIIa receptor transgenic mice where administration of complexes between heparin, Bevacizumab and heparin-binding isoforms of its VEGF-A target lead to platelet aggregation and thrombosis (Meyer, T. et al. J. Thromb. Haemost. 2009, 7: 171-181). Angiocal was tested in the same model and does not cause any of these adverse effects on platelets in vivo. GLP toxicology studies with Angiocal were performed in two relevant species to determine the NOAEL. In addition, we did not observe effects on inflammatory cytokines or complement factors in these studies while exaggerated pharmacodynamic effects consistent with potent VEGF neutralization were seen. Angiocal is currently undergoing phase Ib clinical testing in cancer patients to establish Anticalins as novel and safe class of therapeutic molecules. 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 3632. doi:10.1158/1538-7445.AM2011-3632
Endoscopic Ultrasound-Guided Fine Needle Aspiration In The Diagnosis Of Gastrointestinal Stromal Tumours
Authors: TS Chua, A Kwek
Journal: Endoscopy (2006)

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. The accurate diagnosis of GISTs require positive immunohistochemistry staining for c-kit (CD 117) expression, in the setting of an appropriate microscopic appearance of the tumour. Obtaining tumour samples for analysis is therefore critical to diagnosis and subsequent therapy.
Stat Bite: Use of Lumpectomy for Breast Cancer
Authors: L. Ries
Journal: JNCI Journal of the National Cancer Institute (1995)

Stat Bite : Use of Lumpectomy for Breast Cancer Get access Lynn Ries Lynn Ries NCI Surveillance Program Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 5, 1 March 1995, Page 339, https://doi.org/10.1093/jnci/87.5.339 Published: 01 March 1995
Inverted sessile serrated polyp diagnosed by magnifying image-enhanced colonoscopy
Authors: T. Muramoto, Y. Oono, K.-I. Fu, H. Ikematsu, T. Yano, T. Kojima, K. Minashi, K. Kaneko
Journal: Endoscopy (2011)

Recently, improved endoscopic imaging and advancements in diagnostic technology, such as magnifying colonoscopy and image-enhanced endoscopy (IEE), including narrow-band imaging (NBI) systems, have provided a higher rate of detection of superficial and small colorectal tumors. Even a depressed colon cancer as small as 5 mm in size can be correctly diagnosed as submucosal deeply invasive carcinoma with magnifying chromoendoscopy and then appropriately treated surgically without endoscopic resection [1]. Furthermore, magnifying chromoendoscopy can differentiate between colorectal neoplastic and non-neoplastic polyps [2]. We report a case of a depressed lesion, about 8 mm in diameter, which was diagnosed as an inverted sessile serrated polyp (SSP) by magnifying image-enhanced colonoscopy before removal.
Case 17-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.M. Stone, L. Quintanilla
Journal: New England Journal of Medicine (1992)

Presentation of CaseAn 80-year-old man was admitted to the hospital because of repeated bouts of hematochezia during several hours before entry.The patient was in stable health until two or three days earlier, when he experienced crampy pain in both lower abdominal quadrants that lasted for several minutes. At 4 a.m. on the day of admission he passed a stool and observed gross blood in the toilet. Later in the morning he passed four more semiformed stools, each accompanied by gross blood, and in addition soiled his undergarments twice with blood that he passed without ability to control his . . .
O08 * HAEMATOLOGICAL TOXICITIES IN CRANIOSPINAL RADIOTHERAPY: A 10-YEAR REVIEW
Authors: K. Chua, Y. C. Chang, M. N. Gaze, S. C. Short, N. Fersht
Journal: Neuro-Oncology (2014)

INTRODUCTION: To study the nature of haematological toxicities during craniospinal irradiation and correlate clinical factors with severity of these toxicities. METHOD: We examined treatment charts of patients who underwent craniospinal irradiation between 2003 and 2014. Clinical factors such as diagnosis, age, radiation dose and chemotherapy were noted. Blood counts before, during and after craniospinal irradiation were studied. Toxicities were scored according to Common Toxicity Criteria Adverse Events Version 3. RESULTS: A total of 93 patients were identified with a median age of 13 years. Median craniospinal dose was 30Gy. 55 patients received chemotherapy - 34 concurrent and 21 neoadjuvant. Counts fell from onset of craniospinal and nadirs occurred most frequently in week 2 for neutrophils and haemoglobin and week 3 for platelets. 22.6% patients suffered grade 3 or 4 toxicity. Baseline haemoglobin was the only independent predictor for severe anaemia with odds ratio of 0.338 (95%CI 0.148-0.775, P < 0.001). Similarly, chemotherapy predicted for severe neutropaenia with odds ratio of 0.091 (95%CI 0.009-0.965, P = 0.047). Baseline platelet levels predicted for severe thrombocytopaenia with an odds ratio of 0.99 (95%CI 0.983-0.998, P = 0.011). A combination of blood nadir levels, age and chemotherapy strongly correlated with neutrophil (R = 0.519,P < 0.001) and haemoglobin nadir levels (R = 0.803,P < 0.001). As for platelet nadir levels, only baseline platelets had a strong correlation (R = 0.542, P < 0.001). CONCLUSION: Our study confirms that baseline levels, age and chemotherapy predict for severe haematological toxicities and validate our close monitoring and supportive management of patients with these high-risk features.
REM sleep and dreaming functions beyond reductionism
Authors: Roumen Kirov
Journal: Behavioral and Brain Sciences (2013)

Abstract Brain activation patterns and mental, electrophysiological, and neurobiological features of rapid eye movement (REM) sleep suggest more functions than only elaborative encoding. Hence, the periodic occurrence of REM sleep episodes and dreaming may be regarded as a recurrent adaptive interference, which incorporates recent memories into a broader vital context comprising emotions, basic needs and individual genetic traits.
PTH-086 Refractory coeliac disease outcomes in a single centre
Authors: S C Donnelly, C M Ho-Yen, T Mitchell, F Chang, H J Ellis, P J Ciclitira
Journal: Gut (2010)

<h3>Introduction</h3> The aim of this study is to describe the clinical outcomes of those patients in UK tertiary referral centre referred with a diagnosis of refractory coeliac disease (RCD). This is compared to the grim multicentre survival data12 in current literature- 5-year survival RCD type 1 96% and type 2 44%. <h3>Methods</h3> Patients were entered into a database from clinic letters. Notes were reviewed for patient demographics, past medical history with dates, drug history and dietetic input and clinical course. The hospital electronic computer system was trawled for clinical parameters at time of diagnosis and during subsequent follow-up. <h3>Results</h3> Review of 32 of the 44 patient notes was able to be done and 12 patients were found to have true RCD. 4 patients had RCD type 1 and 8 patients had RCD type 2. The follow-up range (mths) was as follows type 1 3–56, type 2 3–96 and the age range (years) type 1 28–74, type 2 44–79. There is one primary enteropathy associated T-Cell lymphoma in the type 2 group who has undergone resection and CHOP chemotherapy in 1997. The HLA type II status is known for 9 of the 12 RCD patients. Type1 RCD have 1 DQ2 and 1 heterogeneous DQ2/DQ8 whereas type 2 RCD have 4 DQ2 and 3 DQ8. All RCD patients had normal albumen and haemoglobin at time of presentation. Four of the RCD type 2 patients changed to type 1 with steroids and azathioprine, however none of the type 1 RCD improved histologically. All RCD patients are alive to date. 20 non-responsive coeliac disease patients were found to have the following diagnoses: normal treated coeliac disease 4, not on gluten free diet (GFD) 6, small bowel bacterial overgrowth 10, lactose intolerance 2, Crohn9s disease 1. <h3>Conclusion</h3> Compared to the current literature available with grim prognosis for type 2 RCD, our patient data would not support this. Part of the discrepancy is perhaps to do with the use of T-cell receptor in the diagnosis of RCD which was not used in reference 2. Interestingly there is a high DQ8 penetrance which may implicate a different mechanism driving RCD. More numbers are required to be analysed however our evidence supports treatment with steroids and azathioprine.
OP0171 A data driven approach to the definition of a positive MRI of the sacroiliac joints in spondyloarthritis:
Authors: U. Weber, V. Zubler, S.J. Pedersen, K. Rufibach, R.G. Lambert, S. Chan, M. Ostergaard, W.P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Inflammation on magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) in patients with spondyloarthritis (SpA) is a major criterion in the Assessment of SpondyloArthritis (ASAS) classification criteria for axial SpA, which are based on expert clinical opinion as gold standard. The definition of a positive SIJ MRI in the ASAS criteria was generated by consensus among experts. Studies using a data-driven approach to defining a positive SIJ MRI are scarce. <h3>Objectives</h3> To generate candidate definitions for a positive MRI based on confidence in the diagnosis of SpA by expert MRI readers. <h3>Methods</h3> The study population comprised 220 consecutive patients with back pain ≤50 years newly referred to 2 university clinics, and 79 healthy controls. Patients were classified according to clinical examination and pelvic radiography as having non-radiographic axial SpA (nr-axSpA) (n=74), ankylosing spondylitis (n=60), or mechanical back pain (n=86). SIJ MRI were assessed independently in random order by 4 blinded expert readers according to a standardized module that records SpA features (bone marrow edema (BME), erosion (ER), fat infiltration (FI)) on MRI. Readers recorded their level of confidence in the diagnosis of SpA by global evaluation of the MRI scan on a 0-10 scale (0 = definitely not SpA; 10 = definite SpA). Assignment of a definitive diagnosis of SpA was pre-specified as the majority (at least 3 of 4) of readers recording definite SpA with a confidence level of 8-10. Absence of SpA required all 4 expert readers to record non-SpA (≤4 on 0-10 scale). We estimated the type and extent of involvement according to number of affected SIJ quadrants attaining specificity of 90% and 95% for SpA and corresponding sensitivity. The corresponding area under the curve (AUC) was computed by receiver operating curves using the number of affected SIJ quadrants. <h3>Results</h3> 86 subjects met the MRI criterion of definite SpA (≥3 readers scoring ≥8 on 0-10 scale of confidence), and 151 subjects had no SpA (score of ≤4 by all 4 readers). <h3>Conclusions</h3> ER in 1 SIJ quadrant or BME in 3 SIJ quadrants yielded a specificity of over 90% for a positive SIJ MRI and the combination increased sensitivity, compared to ASAS definition, without reducing specificity. This combination represents the best candidate definition for a positive SIJ MRI in SpA for incorporation into future classification criteria. <h3>Disclosure of Interest</h3> None Declared
Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma
Authors: Hidenari Hirata, Keishi Sugimachi, Hisateru Komatsu, Masami Ueda, Takaaki Masuda, Ryutaro Uchi, Shotaro Sakimura, Sho Nambara, Tomoko Saito, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Shuhei Ito, Kotaro Terashima, Katsumi Sakamoto, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori
Journal: Cancer Research (2016)

Abstract Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265–76. ©2016 AACR.
PTU-183 Sehcat – Cast a Wider Net: Abstract PTU-183 Table 1
Authors: B Kok, A Mistry, R Malhotra, J Burdsall, M Hall, R Ransford, A Milestone
Journal: Gut (2013)

<h3>Introduction</h3> Bile acid malabsorption (BAM) is a common cause for chronic diarrhoea in patients with risk factors. The diagnosis is usually confirmed by SeHCAT scan demonstrating lack of retention of radiolabelled bile acid. Treatment with bile acid sequestrants may improve diarrhoea symptoms. We report our experience of using SeHCAT in the investigation of patients with chronic diarrhoea and patient response to therapy. <h3>Methods</h3> Over a 30 month period January 2009- June 2012, all patients who underwent a SeHCAT scan were identified. Patient records and blood results/radiological imaging/endoscopy procedures performed prior to SeHCAT were reviewed. An abnormal SeHCAT result was defined by bile acid retention &lt; 8%. Equivocal results of 8–15% retention were regarded as normal. <h3>Results</h3> 112 patients underwent a SeHCAT scan during this period. 4 patients were excluded due to unavailability of patient records. 53 patients (49%) had abnormal SeHCAT retention. In the remaining 55 patients bile acid retention ranged from 8.1% to 76.8%. BAM was diagnosed in 8 out of 17 patients with a possible Type I abnormality (terminal ileal disease/resection or previous pelvic radiotherapy), 27 out of 66 patients with a possible Type II abnormality (idiopathic) and 18 out of 25 patients with a possible Type III abnormality (post-cholecystectomy). Additional patient demographics are represented in Table 1. The incidence for BAM was highest in the cohort of patients who were post-cholecystectomy, with 71% of all suspected Type III BAM patients having abnormal SeHCAT. However, in terms of absolute numbers, idiopathic BAM formed the highest proportion for abnormal SeHCAT. Interestingly, a wide age variation was experienced across the three groups with proven BAM. The age range in Type I was 36–71 years, in Type II 37–74 years and in Type III 26–80 years. 57% of patients with proven BAM had documented improvement in their diarrhoea frequency and consistency on treatment with a bile acid sequestrant (eg colestyramine). Average reduction of stool frequency was from 7 times/day to 3 times/day. <h3>Conclusion</h3> These results show that BAM is a relatively common problem. It occurs for a variety of reasons and should be thought of earlier in the investigative algorithm, independent of age. In our cohort, a history of post-cholecystectomy chronic diarrhoea was the most likely risk factor associated with BAM, hence this group may particularly benefit from earlier use of SeHCAT scan. Clinical response to colestyramine in BAM was high, although data on long-term compliance/response was not available. <h3>Disclosure of Interest</h3> None Declared.
Accumulation of Bone-Seeking Agent in a Patient With Mediastinal Seminoma
Authors: Dae-Weung Kim, Sang-Ah Jung, Soon-Ah Park, Chang-Guhn Kim
Journal: Clinical Nuclear Medicine (2010)

A 39-year-old man presented with substernal pain and shortness of breath. Bone scan revealed a large soft-tissue uptake in anterior chest. Subsequent computed tomography showed a large mass lesion with well demarcated margins in anterior mediastinum. Percutaneous core needle biopsy and histopathologic examination diagnosed the mediastinal seminoma. Bone scintigraphy could delineate a wide spectrum of nonosseous disorders. The recognition of extraskeletal uptake of bone-seeking agent can enhance the diagnostic value of bone scintigraphy.
Occupation as a Carcinogen: Federal Researcher Suggests Change in Cancer Registries
Authors: J. Randal
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Occupation as a Carcinogen: Federal Researcher Suggests Change in Cancer Registries Get access Judith Randal Judith Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 23, 7 December 1994, Pages 1748–1750, https://doi.org/10.1093/jnci/86.23.1748 Published: 07 December 1994
Abstract 4165: Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion.
Authors: Hye Sook Han, Jieun Yun, Ok-Jun Lee
Journal: Cancer Research (2013)

Abstract Circulating cell-free microRNAs (miRNAs) have been identified as potential noninvasive biomarkers in cancer. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE). We have also analyzed the expression of carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1, which are the most commonly used tumor markers in pleural effusion. Cell-free miRNA expression was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (10 BPEs and 10 LA-MPEs). The PANArrayTM miRNA expression profiling kit (PANAGENE, INC. Daejeon, Korea) was used to identify candidate miRNAs in the discovery set. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA-MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs, CEA, and CYFRA 21-1. Microarray profiling showed that miR-198 was significantly downregulated in LA-MPE compared with BPE (P = 0.002). The miRNA microarray analysis results were confirmed by qRT-PCR (P &amp;lt; 0.001) using the validation set. miR-198 showed an AUC of 0.887, with a sensitivity of 71.1% and a specificity of 95.2%. The AUC for CEA was 0.898, with a sensitivity of 78.4% and a specificity of 97.5%. The AUC for CYFRA 21-1 was 0.836, with a sensitivity of 78.4% and a specificity of 82.5%. The diagnostic performance of miR-198 was comparable with that of CEA, but better than that of CYFRA 21-1. The AUC for all three markers combined was 0.926 (95% confidence interval, 0.843-0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study shows that expression of miR-198 was significantly downregulated in LA-MPE compared with BPE, and combination of cell-free miR-198, CEA and CYFRA 21-1 can be used to differentiate LA-MPE from BPE with a high degree of accuracy. These results suggest that miR-198 in pleural effusions may be a potential diagnostic biomarker for discriminating between BPE and LA-MPE. Citation Format: Hye Sook Han, Jieun Yun, Ok-Jun Lee. Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4165. doi:10.1158/1538-7445.AM2013-4165