tbuckley/cabot-search huggingface dataset:
Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583 [see comments]
Authors: H Ozer, SL George, CA Schiffer, K Rao, PN Rao, DH Wurster-Hill, DD Arthur, B Powell, A Gottlieb, BA Peterson
Journal: Blood (1993)
Breast Cancer Center: Improving Access to Patient Care
Authors: Jatinder Singh, Stephen B. Edge, Ermelinda Bonaccio, Kathleen Trapp Schwert, Brian Braun
Journal: Journal of the National Comprehensive Cancer Network (2014)

To improve access for patients to the Breast Cancer Center at Roswell Park Cancer Institute, the Opportunities for Improvement Project team defined 3 goals: reduce the delay to initial appointment, reduce delays in treatment at the Breast Cancer Center, and reduce delays in the start of endocrine therapy. The team developed a set of tools using Lean methodology that helped to address variables contributing to inefficiencies that result in delays. The idea behind these tools was to integrate all the business variables, such as volume, clinical space, physician availability, services offered in the Breast Program, and patient types, to produce a system or schedule that is more predictable. A new schedule for physicians, independent mid-level clinics, a survivorship program, a primary nursing model, and new roles and responsibilities were defined and implemented. Mean scores in a Press Ganey survey for wait-time questions improved by 10 points, and patient complaints decreased by almost 40%. The team concluded that delays in the Breast Program were symptoms of a larger dysfunction in systems. Fixing the problems required a comprehensive approach to review all the variables that resulted in delays.
Abnormal Myelocytic Cell Development in Interleukin-2 (IL-2)–Deficient Mice: Evidence for the Involvement of IL-2 in Myelopoiesis
Authors: Tannishtha Reya, Nikhat V. Contractor, Matthew S. Couzens, Mariusz A. Wasik, Stephen G. Emerson, Simon R. Carding
Journal: Blood (1998)
Long Non-Coding RNAs in the Cytoplasm
Authors: Farooq Rashid, Abdullah Shah, Ge Shan
Journal: Genomics Proteomics & Bioinformatics (2016)

An enormous amount of long non-coding RNAs (lncRNAs) transcribed from eukaryotic genome are important regulators in different aspects of cellular events. Cytoplasm is the residence and the site of action for many lncRNAs. The cytoplasmic lncRNAs play indispensable roles with multiple molecular mechanisms in animal and human cells. In this review, we mainly talk about functions and the underlying mechanisms of lncRNAs in the cytoplasm. We highlight relatively well-studied examples of cytoplasmic lncRNAs for their roles in modulating mRNA stability, regulating mRNA translation, serving as competing endogenous RNAs, functioning as precursors of microRNAs, and mediating protein modifications. We also elaborate the perspectives of cytoplasmic lncRNA studies.
Duodenal Obstruction by Gallstones (Bouveret’s Syndrome): a Review of the Literature
Authors: A. S. Lowe, S. Stephenson, C. L. Kay, J. May
Journal: Endoscopy (2005)

Gallstone ileus accounts for 1-3 % of cases of obstructing ileus that require surgery, and is estimated to complicate 0.3 - 4.0 % of all cases of cholelithiasis [1] [2]. The level of obstruction is usually at the terminal ileum (60 - 70 %), proximal ileum (25 %), or distal ileum (10 %). Obstruction in the distal jejunum occurs in 9 % of cases, in the colon in 4 %, in the rectum in 2 %, and in the duodenum in only 1 - 3 % [2] [3]. As a general rule, the larger the stone, the more proximal the obstruction. Bouveret's syndrome, first described in 1896 [4], is gastric outlet obstruction following the passage of a gallstone from the gallbladder to the duodenum via a cholecystoduodenal or choledochoduodenal fistula; it is therefore a rare condition. A case is shown in Figures [1] [2] [3] [4].
P72 Low rates of testing for delta hepatitis amongst a large hepatitis B cohort
Authors: B Smith, I Brown, D Muir, P Nutter
Journal: Gut (2010)

Introduction  Delta hepatitis is frequently neglected amongst hepatitis guidelines and publications. There are limited data on the prevalence of delta in the UK and this is likely to be a rapidly evolving area.  Aim  The aim was to examine the rate of testing for delta hepatitis amongst all HBsAg (+) patients seen over a 3 year period in the large liver unit at St Mary9s Hospital (SMH), London. Clinical characteristics of delta (+) patients were reviewed.  Method  All HBsAg (+) results generated from the virology department from Jan 1 2007 to Dec 31 2009 were recorded. Duplicate, indeterminate and untraceable requests were excluded and the number of HBsAg (+) patients that reached hepatology specialist care established. All delta serology requests (ELISA) over the 3 year period were also reviewed. Further trawl of histology and clinical databases was made to identify any delta (+) patients diagnosed prior to 2007. The medical notes of delta (+) patients were reviewed.  Results  858 HbsAg (+) patients were identified that were seen in specialist hepatology clinics in the trust over the 3 years. Of these, only 56 had been tested for delta (6.5%). Delta Ab was (+) in four patients (7.1%). Delta testing was predominantly done in patients with abnormal liver function and low HBV DNA levels. A total of 13 delta (+) patients were found after the subsequent review of virology and histology records from 2000 onwards. Patients were young (mean age 36) with advanced disease (cirrhosis in 55%). The 13 patients were of varied ethnicity, having been born in 10 different countries.  Conclusion  The rate of testing for delta was extremely low. The positivity rate was also low but equivalent to the rate reported amongst another London cohort where universal delta testing is undertaken amongst HBsAg (+) patients (Cross  et al J Med Virol  2008). If the prevalence of delta is similar between the 2 London centres then 8.5% of the 858 patients at SMH would be expected to be delta (+) equivalent to 73 patients, rather than the four found during the 3 years of study. Prospective universal testing for delta is recommended to determine whether there is significant underdiagnosis occurring.
FRI0525 Early Sacroiliitis and Progression to Ankylosing Spondylitis is Associated to Positive HLA-B27 in Juvenile Spondyloarthritis:
Authors: M.O. Perez, N.E. Aikawa, S. Carrasco, C.G. Saad, P.D. Sampaio-Barros, C.R. Gonçalves, J.C.B. Moraes, C. Goldenstein-Schainberg
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Axial and peripheral involvement, enthesitis and positive HLAB27 in 60-90% children are main features of juvenile spondyloarthritis (JSpA). Radiological sacroiliitis represents an important prognostic factor that may occur within 10 years from onset. <h3>Objectives</h3> To determine initial and long term clinical profiles of Brazilian patients with JSpA from a single tertiary university center; the prevalence of HLAB27 and correlation with disease progression to ankylosing spondylitis (AS), according to ASAS criteria. <h3>Methods</h3> Descriptive cross-sectional study of a cohort of JSpA patients. All clinical demographic and radiological data were collected from chart review and HLA-B27 was analysed by flow cytometry (Becton Dickinson). Fisher and McNemar9s tests were used for statistical analyses and p&lt;0.05 considered significant. <h3>Results</h3> Fifty patients with JSpA were assessed, with mean age=31.5±11.1yrs (15-60), mean age at.2±2.73yrs (7-16), mean age at diagnosis=19.8±9.0yrs (7-44) and mean disease duration=18.9±11.4yrs (3-44). The majority were males (44M:6F,88%) and whites (n=42,84%). Eleven (22%) subjects had a 1st-degree relative with SpA and 87% (34/39) were HLAB27+. At diagnosis (Table), peripheral manifestations was predominant, particularly asymmetric oligoarthritis while axial involvement was mainly inflammatory back and buttocks pain; 21 (42%) had enthesitis, all at the Achilles insertion; anterior uveitis was the major extra-articular manifestation. After a mean follow up period of 12.8±9.13yrs (1-45), 5 patients were lost, axial involvement prevailed, enthesitis remained in 13/21 and none had uveitis (Table). Radiological sacroiliitis developed in 96% (n=48) patients: 42% (n=20) ≤5yrs, 17% (n=8) within 6-10yrs and 42% (n=20) &gt;10yrs of initial symptoms. Of note, HLA-B27+ children had earlier sacroiliitis ≤5yrs from diagnosis (p=0.02), high ESR at diagnosis (p=0.04) and developed AS (p=0.02). Regardless of daily NSAIDs therapy intake by all patients, sacroiliitis progression was not prevented (p&gt;0.05). Sulfasalazine was used by 86% and MTX by 72%, and currently 49% patients are on anti-TNF drugs. <h3>Conclusions</h3> Brazilian JSpA patients are characteristically white males with initial peripheral joint and enthesitic manifestations that develop axial disease. The high prevalence of HLAB27+ in JSpA associated to early sacroiliitis, elevated ESR at diagnosis and progression to AS strengthen its role as a genetic marker of disease severity in children. <h3>Disclosure of Interest</h3> None declared
Case 3-1964
Authors: Philip K. Bondy, Richard B. Cohen
Journal: New England Journal of Medicine (1964)

Presentation of Case First admission. A seventy-four-year-old man was admitted to the hospital because of hematuria.One week previously the patient entered another hospital because of prostatism and hematuria and underwent suprapubic prostatectomy, with removal of benign, hypertrophied tissue weighing 106 gm. Four days later bright-red blood was passed through the indwelling catheter; transfusions were given. On the day of admission hematuria recurred, and he was transferred to this hospital.There was no history of previous abnormal bleeding. Five years before admission a left pneumonectomy was performed because of squamous-cell carcinoma; 1 of 12 hilar lymph nodes contained a metastasis. . . .
Relationship between intravenous (IV) busulfan pharmacokinetics (PK) and patient characteristics in allogeneic stem cell transplant patients.
Authors: Ashley Erickson Simmons, Meredith Deal Keisler, Anastasia Ivanova, Kamakshi V. Rao, Thomas C. Shea, Christine Marie Walko
Journal: Journal of Clinical Oncology (2013)

e13507 Background: Busulfan is an alkylating agent commonly used for myeloablation in hematopoietic stem cell transplantation (SCT). Narrow therapeutic index and 2-3 fold interpatient PK variability underscores the need to further explore predictors of busulfan clearance. This analysis aimed to determine patient (pt) characteristics that may impact the clearance of busulfan. Methods: This retrospective analysis assessed allogeneic SCT pts who received a test dose of 0.8 mg/kg IV busulfan, dosed by adjusted body weight, over 2 hours on days -15 to -10 prior to conditioning therapy containing therapeutically dosed busulfan. All pts were treated between June 2004 and July 2012 at the University of North Carolina at Chapel Hill. Noncompartmental PK parameters were calculated from this test dose using Phoenix WinNonlin Pharsight software. A linear model with log of busulfan test dose clearance as an outcome and pt characteristics that included disease state, bone marrow donor type, gender, race, ethnicity, body surface area (BSA), body mass index, type of anticonvulsant prophylaxis used (levetiracetam or phenytoin), total bilirubin and serum creatinine was fit. Results: The study reviewed a total of 88 pts with a mean age of 41.1 (range 18-63). The analysis included 54 males, 76 Caucasians, and 5 African Americans (AA). Seizure prophylaxis with levetiracetam was given to 27 pts, and 51 received phenytoin. After adjusting for pt characteristics, a unit increase in BSA was associated with 0.69 (p = &lt; 0.001) increase in log(clearance). Regression coefficients for phenytoin use with no seizure prophylaxis as reference and for African American race with Caucasian race as reference were significant (0.22, p = 0.033, and -0.31, p=0.13, respectively). No correlation was seen for age (p = 0.357), gender (p = 0.337), levetiracetam use (p = 0.3525), or for any other variable. Conclusions: Our data suggests that higher BSA and phenytoin use are associated with a higher busulfan clearance, while AAs have a lower clearance. These findings may help inform future dosing strategies in order to decrease interpatient PK variability and accurately predict plasma concentrations of busulfan.
Myocardial Atrophy and Chronic Mechanical Unloading of the Failing Human Heart
Authors: Nikolaos A. Diakos, Craig H. Selzman, Frank B. Sachse, Josef Stehlik, Abdallah G. Kfoury, Omar Wever-Pinzon, Anna Catino, Rami Alharethi, Bruce B. Reid, Dylan V. Miller, Mohamed Salama, Alexey V. Zaitsev, Junko Shibayama, Hui Li, James C. Fang, Dean Y. Li, Stavros G. Drakos
Journal: Journal of the American College of Cardiology (2014)
Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product
Authors: A Kuriu, H Ikeda, Y Kanakura, JD Griffin, B Druker, H Yagura, H Kitayama, J Ishikawa, T Nishiura, Y Kanayama
Journal: Blood (1991)
Pharmacokinetics of Hydroxyurea in Young Children with Sickle Cell Anemia: A Report from the BABY HUG Trial.
Authors: Zora R. Rogers, Bruce Thompson, Russell E. Ware, Winfred C. Wang, Rathi V. Iyer, Scott T. Miller, Caterina Minniti, Sohail Rana, Julio C. Barredo, Stuart Toledano, Sherri A. Zimmerman, James F. Casella, Beatrice A. Files, Myron A. Waclawiw, A. Russell Gerber, Duane R. Bonds
Journal: Blood (2005)
Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries
Authors: Stefano Coli, Marco Magnoni, Giuseppe Sangiorgi, Massimiliano M. Marrocco-Trischitta, Giulio Melisurgo, Alessandro Mauriello, Luigi Spagnoli, Roberto Chiesa, Domenico Cianflone, Attilio Maseri
Journal: Journal of the American College of Cardiology (2008)
Clinicopathological impact of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors.
Authors: Midori Ishii, Yoshiyuki Suehara, Keisuke Akaike, Kenta Mukaihara, Daisuke Kubota, Taketo Okubo, Tatsuya Takagi, Takashi Yao, Kazuo Kaneko, Tsuyoshi Saito
Journal: Journal of Clinical Oncology (2015)

10536 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in gastrointestinal tract. Approximately 85-90% of GISTs are harboring oncogenic mutations in KIT or PDGFRA, and the tyrosine kinase inhibitor (TKI) drastically improved the prognosis of GISTs patients. On the other hand, a subset of GISTs acquire secondary resistance to TKI or show primary resistance to TKIs. Recent studies report that the disorder of the protein phosphatase 2, regulatory subunit A, alpha (PPP2R1A) is responsible for the constitutive phosphorylation of its substrates including TKs, and the constitutive phosphorylation of TKs plays an important role in the tumorgenesis and the progression of ovarian and uterine carcinomas. The aim of this study was to elucidate the frequency of PPP2R1A mutations and their impact on the clinicopathological factors in GISTs. Methods: Ninety-six cases of GISTs (formalin-fixed paraffin-embedded material) with prognostic information were collected. These cases were examined for PPP2R1A mutations (exon 5 and 6) by PCR followed by direct sequences, and the impacts of PPP2R1A mutations on the clinicopathological features were examined. In addition, PPP2R1A mutated GISTs were also examined for the mutation status of KIT, PDGFRA and KRAS. Results: Seventeen cases (17.7%) of GISTs harbored mutations in PPP2R1A, and types of mutations were various. Among 17 cases, 15 cases (88.2%) harbored either KIT or PDGFRA mutations, and one case had point mutations in both KIT and PDGFRA. Among two cases of KIT/PDGFRA mutation-negative GISTs, one cases showed KRAS mutation. GIST cases with PPP2R1A mutations had a tendency for shorter disease free survival (DFS) and overall survival (OS) rate, respectively (p < 0.05; DFS, p < 0.05; OS). Conclusions: These results suggest that PPP2R1A mutations play an important role in the tumor progression of GISTs. The effect of PPP2R1A alterations on the phosphorylation status of TKs including KIT and PDGFRA are under evaluation.
A phase II clinical trial of a novel combinatorial antitumor immunotherapy for patients with high-risk resected stage III and metastatic melanoma.
Authors: A. I. Riker, L. C. Alsfeld, M. Harrison, D. Foxworth, Q. Lee, G. R. Rossi, L. Tennant, W. J. Ramsey, N. N. Vahanian, C. J. Link
Journal: Journal of Clinical Oncology (2010)

8586 Background: Patients with advanced melanoma have a uniformly poor outcome, despite all current treatment modalities. Cancer immunotherapy is designed to activate the host immune system and destroy viable tumor cells, often through novel immunologic combinatorial approaches. We hypothesize that such an approach can be an effective treatment option for patients with high-risk resected stage III, recurrent, refractory or stage IV melanoma. Methods: We designed a phase II clinical trial comprised of the HyperAcute Melanoma (HAM) vaccine (NewLink Genetics Corp.) combined with PEG-Intron (Schering-Plough Corp.). Trial design consists of a 12-week regimen, the first 4 weeks with HAM vaccine alone (intradermally) followed by weeks 5-12 with HAM vaccine + PEG-Intron (once weekly, subcutaneously at 6 μ g/kg). Trial endpoints include correlative studies for observed anti-tumor effect and secondarily to determine the overall safety and response rates. Planned sample size is 25 patients. Results: A total of 15 patients have enrolled, with 12 completing the trial and 3 in active treatment. RECIST criteria was utilized for 12 evaluable patients, with 5 developing progressive disease, 5 with no evidence of disease, one with a complete response and one with an ongoing partial response of > 12 months, with marked regression of metastatic disease. Relapse-free interval ranges from 15 months to 3 months. The development of autoimmune antibodies (anticardiolipin, antithyroglobulin) following the completion of the trial was seen in all 11 patients (first patient not evaluated). Vitiligo has developed in 4/12 patients, correlating with 2 patients who developed clinical tumor regression. Conclusions: The combined immunotherapy of advanced melanoma patients with PEG-Intron and HAM Vaccine shows evidence of synergistic immune activation that translates into clinical efficacy as seen with tumor regression combined with development of autoimmune antibodies and vitiligo. However, we will need to await final analysis of all patients to determine the ultimate significance of host immune activation as it relates to tumor regression in melanoma patients with advanced disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NewLink Genetics NewLink Genetics NewLink Genetics, Schering-Plough
Syringe-transmitted Jaundice
Authors: R. S. Morton
Journal: BMJ (1948)

IINOCULAT1ION HEPATITISBMICTISH MEDICAL JOURNAL are used for venepuncture.At blood-sampling for the sedi- mentation test we must also calculate with the presence of this risk.The risk of infection can be eliminated in two ways: (1) by the use of sterile needles alone without syringes at venepunc- ture; (2) by the provision of a sufficient number of syringes to enable a fresh sterilized instrument to be used for every patient.
Fc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer
Authors: Geoffrey Liu, Dongsheng Tu, Marcia Lewis, Dangxiao Cheng, Leslie A. Sullivan, Zhuo Chen, Eric Morgen, John Simes, Timothy J. Price, Niall C. Tebbutt, Jeremy D. Shapiro, G. Mark Jeffery, J. Daniel Mellor, Thomas Mikeska, Shakeel Virk, Lois E. Shepherd, Derek J. Jonker, Christopher J. O'Callaghan, John R. Zalcberg, Christos S. Karapetis, Alexander Dobrovic
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Two germline Fc-γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A;His(H)131Arg(R)] and rs396991 [FCGR3A;Phe(F)158Val(V)] produce altered proteins through amino acid substitutions; both are reported to be associated with cetuximab-related outcomes. We performed a validation of these polymorphisms in NCIC CTG CO.17, a randomized trial of cetuximab monotherapy in refractory, metastatic colorectal cancer expressing EGFR. Experimental Design: DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped. In addition to log-rank tests, Cox proportional hazard models assessed their relationships with overall (OS) and progression-free survival (PFS), adjusting for clinically important prognostic factors, along with a polymorphism–treatment arm interaction term. Results: Somatic KRAS status was wild-type for exon 2 in 153 (52%) of 293 patients, from whom tumor DNA was available. For FCGR2A H/H, a genotype–treatment interaction for KRAS wild-type patients was observed for OS (P = 0.03). In KRAS wild-type patients carrying FCGR2A H/H, cetuximab (vs. no cetuximab) improved survival substantially, with adjusted HRs (aHR) of 0.36 (OS) and 0.19 (PFS) and absolute benefits of 5.5 months (OS; P = 0.003) and 3.7 months (PFS; P = 0.02). In contrast, patients carrying FCGR2A R alleles (H/R or R/R) had aHRs of only 0.78 (OS; 2.8-month benefit) and 0.53 (PFS; 1.6-month benefit). No relationships were found for rs396991 (FCGR3A). Conclusions: In the CO.17 trial, cetuximab worked best for patients with KRAS wild-type colorectal cancers carrying FCGR2A H/H genotypes. Significantly lower benefits were observed in patients carrying germline FCGR2A R alleles. Clin Cancer Res; 22(10); 2435–44. ©2016 AACR.
High-Level Clonal <i>FGFR</i> Amplification and Response to FGFR Inhibition in a Translational Clinical Trial
Authors: Alex Pearson, Elizabeth Smyth, Irina S. Babina, Maria Teresa Herrera-Abreu, Noelia Tarazona, Clare Peckitt, Elaine Kilgour, Neil R. Smith, Catherine Geh, Claire Rooney, Ros Cutts, James Campbell, Jian Ning, Kerry Fenwick, Amanda Swain, Gina Brown, Sue Chua, Anne Thomas, Stephen R.D. Johnston, Mazhar Ajaz, Katherine Sumpter, Angela Gillbanks, David Watkins, Ian Chau, Sanjay Popat, David Cunningham, Nicholas C. Turner
Journal: Cancer Discovery (2016)

FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy.
Case 27-1962
Authors: Lloyd H. Smith, Austin L. Vickery
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A twenty-seven-year-old woman entered the hospital because of edema.Four months previously she began to have increasing swelling of the legs in association with generalized weakness, especially in the legs, and with sensations of coldness and paresthesias in the legs. She gained 20 pounds in weight during the next two months. A single episode of paroxysmal nocturnal dyspnea occurred. Persistent diarrhea began three months before entry, with 4 or 5 bowel movements during the day and 3 or 4 at night. One month later bed rest for a week effected a loss of 30 pounds . . .