tbuckley/cabot-search huggingface dataset:
OT-04 * PRIMARY CENTRAL NERVOUS SYSTEM NON HODGKIN LYMPHOMA IN A PEDIATRIC PATIENT WITHOUT IMMUNODEFICIENCY RELATED. CASE REPORT AND LITERATURE REVIEW
Authors: M. R. Aguilar-Ortiz, R. Cardenas-Cardos, L. Velasco-Hidalgo, P.-M. Pasquel-Garcia-Vazquez, R. Rivera-Luna, A. Marhx-Bracho
Journal: Neuro-Oncology (2015)

The central nervous system primary lymphoma is a very infrequent disease in the pediatric population. Currently there are no or few recommendations and/or clinical useful trials to define the best therapeutic option in this population. The objective is to report the case of a child with primary lymphoma of the central nervous system without any associated immunodeficiency, and to do a qualitative review of the literature regarding this disease in children. The possibility of cytogenetic changes has been postulated explaining the heterogeneity in the behavior of this disease, since it has been seen that it is different from other lymphomas in usual presentations. The experience of treatment in pediatric patients with lymphoma, is based on results obtained in adult population, mainly with the use of anti-metabolites such as methotrexate and citarabine. The use of cranial radiation therapy is still controversial and is recommended only in special cases.
Abstract 3399: Detection of rare mutations in plasma by droplet digital PCR
Authors: Austin So, Benjamin Hindson, Ryan Koehler, Serge Saxonov, George Karlin-Neumann, Nolan Ericson, Jason Bielas
Journal: Cancer Research (2012)

Abstract Detection and quantitation of specific mutations in circulating plasma holds promise for earlier and less invasive diagnosis of disease. This presents significant analytical challenges, particularly as the biomarker may differ from its highly abundant wildtype by only a single nucleotide. Conventional methods have poor selectivity and fail to detect mutant sequence below 1 in 100 wildtype sequences. Compounding this, the amount of circulating nucleic acid in plasma is low. Here we present a simple strategy using droplet digital™ PCR (ddPCR™) for the detection of somatic mutations with high selectivity and sensitivity. Based on the simple principle of sample partitioning into water-in-oil microdroplets, this ddPCR method increases the abundance of a mutant DNA sequence up to 20,000 times compared to an equivalent bulk PCR reaction. Using conventional TaqMan chemistries and workflow, selectivities of up to 1/100,000 can readily be achieved in any laboratory. We evaluated ddPCR for the detection and quantitation of several clinically important mutations in the EGFR and KRAS loci from clinical samples derived from normal and tumor plasma samples. We also demonstrate the feasibility of multiplexing of Kras and EGFR assays to improve sample processing efficiency. 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 3399. doi:1538-7445.AM2012-3399
Visualization of a Photopenic Lesion Secondary to a Giant Small Bowel Diverticulum with Fecal Retention During Meckel's Scintigraphy
Authors: T H Young, R Y Shyu, Y C Chao, W S Huang, J C Yan, H S Tang
Journal: Clinical Nuclear Medicine (1998)

A 30-year-old man with a second episode of melena had previous workups, including gastroscopy and colonoscopy, that failed to localize a source of bleeding. Tc-99m pertechnetate abdominal scintigraphy showed a giant photopenic lesion in the suprapubic region. An upper gastrointestinal and small bowel series obtained after Meckel's scintigraphy showed a huge small bowel diverticulum in the midanterior pelvis. This case shows how a giant small bowel diverticulum with fecal retention can produce images suggestive of a photopenic lesion during Meckel's scintigraphy.
AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and<i>ESR1</i>-Mutant Breast Tumors in Preclinical Models
Authors: Hazel M. Weir, Robert H. Bradbury, Mandy Lawson, Alfred A. Rabow, David Buttar, Rowena J. Callis, Jon O. Curwen, Camila de Almeida, Peter Ballard, Michael Hulse, Craig S. Donald, Lyman J.L. Feron, Galith Karoutchi, Philip MacFaul, Thomas Moss, Richard A. Norman, Stuart E. Pearson, Michael Tonge, Gareth Davies, Graeme E. Walker, Zena Wilson, Rachel Rowlinson, Steve Powell, Claire Sadler, Graham Richmond, Brendon Ladd, Ermira Pazolli, Anne Marie Mazzola, Celina D'Cruz, Chris De Savi
Journal: Cancer Research (2016)

Abstract Fulvestrant is an estrogen receptor (ER) antagonist administered to breast cancer patients by monthly intramuscular injection. Given its present limitations of dosing and route of administration, a more flexible orally available compound has been sought to pursue the potential benefits of this drug in patients with advanced metastatic disease. Here we report the identification and characterization of AZD9496, a nonsteroidal small-molecule inhibitor of ERα, which is a potent and selective antagonist and downregulator of ERα in vitro and in vivo in ER-positive models of breast cancer. Significant tumor growth inhibition was observed as low as 0.5 mg/kg dose in the estrogen-dependent MCF-7 xenograft model, where this effect was accompanied by a dose-dependent decrease in PR protein levels, demonstrating potent antagonist activity. Combining AZD9496 with PI3K pathway and CDK4/6 inhibitors led to further growth-inhibitory effects compared with monotherapy alone. Tumor regressions were also seen in a long-term estrogen-deprived breast model, where significant downregulation of ERα protein was observed. AZD9496 bound and downregulated clinically relevant ESR1 mutants in vitro and inhibited tumor growth in an ESR1-mutant patient-derived xenograft model that included a D538G mutation. Collectively, the pharmacologic evidence showed that AZD9496 is an oral, nonsteroidal, selective estrogen receptor antagonist and downregulator in ER+ breast cells that could provide meaningful benefit to ER+ breast cancer patients. AZD9496 is currently being evaluated in a phase I clinical trial. Cancer Res; 76(11); 3307–18. ©2016 AACR.
UTILIZATION, CHARACTERISTICS, AND IN-HOSPITAL OUTCOMES FOR PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING IN-HOSPITAL CORONARY ARTERY BYPASS GRAFTING (CABG)
Authors: Yi Pi, Matthew Roe, DaJuanicia Simon, Karen Chiswell, Lee Garvey, Gregg Fonarow, James de Lemos, Ying Xian
Journal: Journal of the American College of Cardiology (2016)
A Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer.
Authors: A. Forero, M. Saleh, J. Galleshaw, C. Jones, J. Shah, I. Percent, L. Nabell, J. Carpenter, C. Falkson, H. Krontiras, M. Urist, K. Bland, J. De Los Santos, R. Meredith, V. Caterinicchia, W. Bernreuter, J. O'Malley, Y. Li, A. LoBuglio
Journal: Cancer Research (2009)

Abstract Purpose Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods Patients were treated with a neo-adjuvant regimen of letrozole, 2.5mg/day (P.O.) and bevacizumab 15mg/kg Q3 weeks (I.V.) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at 3 week intervals and tumor assessment (physical exam and tumor ultrasound) at 6 week intervals. PET scans were carried out prior to therapy and 6 weeks after initiation of therapy. Surgery was done 4 weeks after the last dose of bevacizumab. Results Twenty five evaluable patients were treated. The regimen was well tolerated except for 2 patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The 4 patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. 8/25 patients (32%) attained stage 0 or 1 status. PET scan response at 6 weeks correlated with clinical CR and breast pathologic CR at 24 weeks (p &amp;lt; 0.0036). Conclusion Combination neo-adjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in impressive clinical and pathologic responses. The Breast Cancer Translational Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1088.
George Chalmers’ portrait of James Lind, 1783-2008: a reconstruction
Authors: Linda Peters, John Hepner
Journal: Journal of the Royal Society of Medicine (2012)

Sir George Chalmers' portrait of James Lind is likely to have been painted in 1783, at the end of Lind's term as Chief Physician at The Royal Hospital, Haslar, which is shown in the background of the picture. The books shown in the picture are Lind on Scurvy,1 which stands upright on Lind on Climate2; and An essay on the most effectual means of preserving the health of seamen,3 which lies open under Lind's left hand. The lettering on the spine of the other book (lying directly on the table) is not legible, but it is presumably Lind's Two papers on fevers and infection.4 The portrait seems likely to have remained at The Royal Hospital Haslar,5 until Edmond Peters, a descendant of James Lind, obtained it at the end of the 19th century or the beginning of the 20th century.

The portrait passed from Edmond Peters to Jack Peters, one of his two sons. Jack and his wife Mabel (nee Palmer) emigrated to South Africa in 1946; but two weeks after the family arrived in Johannesburg, Jack was killed in a road traffic accident, leaving Mabel to cope with two young daughters in a strange country. After Jack's estate had been wound up they moved to Highlands North, a Johannesburg suburb, when their possessions were brought out of storage. However, Mabel disposed of the portrait, together with other antiques, because she was concerned that the heat in South Africa might damage them.

The portrait appears to have been sold in the late 1940s. However, there is no information as to its whereabouts from then until it was purchased in Johannesburg in November 1953 by Kurt and Lorna Hepner. It is not known who the seller was, but it could well have been an art dealer. Since then the portrait has remained in the Hepner family. A note on the back of the portrait in Lorna Hepner's handwriting states that the picture is “signed and dated 1783”, although these details are not obvious in the current framing.

After Lorna Hepner's death, the painting was inherited by her family in England, arriving there late in 2008. Soon after, John Hepner, Lorna's son, discovered The James Lind Library, which contains biographical details about Sir George Chalmers, Lind's portraitist, researched by John Chalmers.6 Because John Chalmers’ article noted (at the time) that the current whereabouts of the portrait were not known, John Hepner contacted him to let him know that the portrait was in the Hepner family's possession, and in England. John Chalmers informed Iain Chalmers, who went to meet the Hepner family with his son Theo Chalmers, a professional photographer, who photographed the portrait for publication in The James Lind Library. Copyright in the painting belongs to John Hepner.
AT-29 * INTRAVENOUS ADMINISTRATION OF TOCA 511 IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: S. Kalkanis, D. J. Jolly, D. Pertschuk, D. Ostertag, J. M. Robbins, T. T. Huang, H. Gruber, T. Mikkelsen
Journal: Neuro-Oncology (2014)

INTRODUCTION: Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector (RRV) that encodes the transgene cytosine deaminase (CD). Subsequent oral administration of investigational extended-release 5-FC (Toca FC) results in formation of 5-FU within infected tumor cells expressing CD. A clinical study was initiated to evaluate the delivery of Toca 511 vector to brain tumor via intravenous administration (NCT01985256). METHODS: The primary purpose of this study is to identify the highest safe and well tolerated dose of Toca 511 administered intravenously to subjects with recurrent high grade glioma scheduled for repeat resection. Subjects who have a recurrent high grade glioma who are scheduled for repeat surgical resection will receive an intravenous administration of Toca 511 approximately 11 days prior to surgery. At the time of surgery Toca 511 will be re-administered into the walls of the resection cavity. After 5 weeks, subjects then take oral Toca FC for 7 days every five weeks until study completion or progression. Dose escalation is accelerated for the first three cohorts (single patient cohorts) and the subsequent two cohorts follow a standard 3 + 3 design. Doses are escalated at half-log increases from a total of 4.8x10^8 to 4.8x10^10 TU. RESULTS: Preclinical studies defined the pharmacokinetics and efficacy of intravenous Toca 511 with intraperitoneal 5-FC in a syngeneic murine brain cancer model. In humans, the first 2 subjects were administered Toca 511 intravenously without complication or toxicity. Peak circulating Toca 511 in the patient in the second dose cohort was present at approximately one billion viral particles per mL of plasma. The half-life of the vector was approximately 5 minutes. Preliminary safety and tolerability data, in addition to pharmacokinetics of Toca 511 in the blood and resected tumor will be reported. CONCLUSION: Toca 511 has been safely administered intravenously and further dose escalation is ongoing.
P2-05-05: Receptor-Like Protein Tyrosine Phosphatase Kappa (PTPRK) and Its Biological Role in Angiogenesis.
Authors: P-H Sun, L Ye, MD Mason, WG Jiang
Journal: Cancer Research (2011)

Abstract Introduction: Protein Tyrosine Phosphatases (PTPs) are known as signalling molecules which affect cell growth, differentiation and oncogenic transformation. PTPs have been indicated in tumourigenesis and progression of various solid tumours. PTPRK, receptor-type protein tyrosine phosphatase kappa, has been shown to down-regulate transcriptional activity of beta-catenin and impact distribution of beta-catenin/E-cadherin complexes on cancer cell membrane. However, the role played by PTPRK in angiogenesis remains unknown. In present study, the effect of PTPRK knock-down on functions and tubule formation ability of HECV cells was investigated. (or In the present study, the effect of PTPRK on angiogenesis process was investigated.) Methods: anti-PTPRK ribozyme transgenes were constructed to knock-down PTPRK expression in vascular endothelial cells, HECV cells. The subsequent effect upon in vitro cell growth, adhesion, migration and microvascular tubule formation was examined using a variety of functional assays. Result: Knock-down PTPRK in HECV cells (HECVΔPTPRK) resulted in a decrease of cell growth in vitro. The growth rate of HECVΔPTPRK was 276.3±16.4, p=0.01 compared with HECVpEF (314.8±21.9) controls. However, knock-down of PTPRK in HECV cells increased cell motility. The cell migration distance of HECVΔPTPRK was 83.8±19.8μm, p=0.008 compared with HECVpEF (61.8±11.8μm) controls. No effect on cell adhesion by PTPRK knockdown was seen in HECVΔPTPRK (81.2±6.6), compared with HECVpEF control (78.8±15.6). Furthermore, knock-down of PTPRK suppressed tubule formation in HECV cells, the length of total tubules (μm) in HECVΔPTPRK was 2167.4±943.2, p&amp;lt;0.05 compared with HECVpEF (3130.6±386.9) control. Conclusion: Knock-down of PTPRK reduced the growth and tubule formation abilities of vascular endothelial cells. It suggests that PTPRK is pivotal regulator for angiogenic process. Further investigations are required to identify the downstream pathways involved in these impacts. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-05.
Monitoring colonoscopy withdrawal times remains important
Authors: M. Rutter, A. Chilton, J. Patnick
Journal: Endoscopy (2012)

We read the recent paper on colonoscopy withdrawal time (CWT) with interest [1]. In the English Bowel Cancer Screening Programme, a diagnostic withdrawal time of at least 6 minutes remains a key quality metric for colonoscopic performance [2]. We feel that it is an important standard, as it helps to protect against the poor practice of rapid withdrawal without proper mucosal inspection. Although a slow withdrawal time is not the only aspect of a gold standard inspection technique, it remains one of its key principles.
EUS-guided drainage of pancreatic fluid collections (PFCs): assessment of outcomes in 132 consecutive patients
Authors: Varadarajulu Shyam
Journal: Endoscopy (2011)

Background: Unlike fine needle aspirations (FNAs), data on the clinical outcomes and complications of EUS-guided drainage of PFCs is limited due to the small number of patients, varied procedural techniques and multiple operators. Aim: Evaluate the treatment outcomes and complications of EUS-guided drainage of PFCs in a large cohort of patients using a standardized technique. Methods: Clinical outcomes of all patients who underwent EUS-guided drainage of PFCs over a 7 year period was assessed from a prospective database. Prior to EUS, an ERCP was attempted for pancreatic stent placement in all patients with a duct disruption. All procedures were performed by one endoscopist using a standard one step dilation technique. At EUS, after coiling a 0.035 inch guidewire and dilating the transmural tract, two or three 7Fr stents were deployed. Additional nasocystic catheters were deployed in patients with abscess or necrotic fluid collections. Results: A total of 132 patients (mean age 49.9yrs, [range 9–76], Male 78) underwent EUS-guided drainage of PFCs that were classified as pseudocyst in 68, abscess 32 and necrosis in 32. Forty nine patients (37.1%) underwent pancreatic stent placement at ERCP. The mean diameter of the PFCs was 94mm (range, 40–220mm) and 23 patients had undergone prior therapy (surgery 7, percutaneous drainage 16). Mean duration of follow-up was 197 days. Successful resolution of symptoms occurred in 86% of patients. Compared to pseudocysts and abscesses, treatment failure rate was higher for drainage of necrotic collections (4.1 vs. 40.6%, p=0.0002). Complication of perforation occurred in 2 patients (frequency 1.5%, 95% CI [0.2%, 5%]), bleeding 1 (0.7%, 95% CI[0.1%, 4%]), infection 6 (4.5%, 95% CI [2.1%, 9.5%]) and stent migration in 1 (0.7%, 95% CI [0.1%, 4%]). There were three deaths from multi-organ dysfunction within 30 days of EUS of which none were procedure related. Conclusions: EUS-guided drainage of pancreatic fluid collections is successful in a majority of patients with a low complication rate. The technique is best suited for drainage of non-necrotic collections.
The Role of Interleukin-1 in Disease
Authors: Franklin H. Epstein, Charles A. Dinarello, Sheldon M. Wolff
Journal: New England Journal of Medicine (1993)

The interleukin-1 family consists of three structurally related polypeptides. The first two are interleukin-1α and interleukin-1β, each of which has a broad spectrum of both beneficial and harmful biologic actions, and the third is interleukin-1-receptor antagonist, which inhibits the activities of interleukin-1. Among the properties of the two forms of interleukin-1 (α and β) is the ability to induce fever, sleep, anorexia, and hypotension. Interleukin-1 stimulates the release of pituitary hormones, increases the synthesis of collagenases, resulting in the destruction of cartilage, and stimulates the production of prostaglandins, leading to a decrease in the pain threshold. Interleukin-1 has also been . . .
PWE-120 How does a blood transglutaminase-based rapid test compare to conventional serological markers to detect coeliac disease?: Abstract PWE-120 Table 1
Authors: M Kurien, K E Evans, I Chalkiadakis, M F Hale, V Courtice, A J Irvine, M Hadjivassiliou, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> Coeliac disease may be missed at endoscopy. For this reason many centres take routine duodenal biopsies or have a low threshold for duodenal biopsy. While duodenal biopsies demonstrating villous atrophy remains the current gold standard, serological markers are widely used either alone or in combination (tissue transglutaminase (TTG)/endomysial antibody (EMA)) to help identify at risk individuals. However, these results may not be available at the time of endoscopy. Recently a whole blood transglutaminase-based rapid test has become available. This Point of Care Test (POCT) can be read in 5–10 min prior to endoscopy and could help in determining which patients having an endoscopy should have a duodenal biopsy. This strategy could also have cost-saving implications if we could reduce the number of duodenal biopsies performed. This is the first study to assess the clinical utility of this POCT within the setting of endoscopy. Comparisons are made against current serological markers and duodenal biopsy. <h3>Methods</h3> Patients undergoing oesophogastroduodenoscopy (OGD) with duodenal biopsies were prospectively recruited between August 2010 and November 2011. Unselected patients undergoing endoscopy were concurrently serologically tested for IgA TTG, EMA, a total IgA immunoglobulin level and the transglutaminase-based rapid test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the transglutaminase-based rapid test were calculated and comparisons made with TTG and EMA to detect coeliac disease, using duodenal biopsy as the gold standard. <h3>Results</h3> 235 patients were recruited (145 female, median age 48, range 17–86). Of these, 51 had newly diagnosed coeliac disease and 184 were controls with a normal duodenal biopsy. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the individual coeliac serological test are demonstrated in Abstract PWE-120 table 1. <h3>Conclusion</h3> The Negative Predictive Value of the transglutaminase-based POCT may allow us to adopt this into clinical practice and potentially reduces the number of duodenal biopsies which would be taken at endoscopy. <h3>Competing interests</h3> None declared.