tbuckley/cabot-search huggingface dataset:
Cardiac mucosa, Barrett's oesophagus and cancer of the gastro-oesophageal junction: what's in a name?
Authors: Stuart Jon Spechler
Journal: Gut (2016)

The pathogenesis of adenocarcinoma of the oesophagus is assumed to start with GORD that damages the oesophageal squamous epithelium while also inducing genetic reprogramming of progenitor cells that proliferate to repair the damage.1 Presumably, this GORD-induced reprogramming of developmental transcription factors causes the progenitors to differentiate into columnar cells with intestinal features, resulting in the squamous-to-columnar metaplasia of Barrett's oesophagus. Barrett's metaplasia, in an environment of oxidative and nitrosative stress from ongoing GORD, is predisposed to develop further genetic alterations resulting in dysplasia and, ultimately, cancer. Thus, oesophageal adenocarcinoma is widely regarded as a consequence of GORD and Barrett's oesophagus in most, if not all cases.

A number of observations have been difficult to reconcile with this popular concept of oesophageal carcinogenesis. Most notably, many patients with oesophageal adenocarcinoma have no evidence of antecedent GORD or Barrett's metaplasia.2 ,3 Rather than abandoning the notion that all oesophageal adenocarcinomas arise from GORD and Barrett's oesophagus, authorities have proposed explanations for the unsupportive observations. The lack of antecedent GORD symptoms can be attributed to poor patient recall or to GORD that causes oesophageal damage without symptoms. The absence of Barrett's metaplasia in the oesophagus of patients with established adenocarcinomas has been dismissed as a consequence of tumour growth obliterating evidence of the precursor metaplasia. Although plausible, these explanations are largely unprovable and highly questionable.

In the stomach, chronic gastritis can lead to adenocarcinoma that is histologically indistinguishable from oesophageal adenocarcinoma. For an adenocarcinoma that straddles the gastro-oesophageal junction (GOJ), therefore, it is often not possible to establish whether the tumour arose from oesophagus or stomach. Consequently, patients with …
Shedding Old Paradigms: Developing Viruses to Treat Cancer
Authors: Emily K. Bergsland, Alan P. Venook
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.9.2220 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11980991 Shedding Old Paradigms: Developing Viruses to Treat Cancer Emily K. BergslandxEmily K. BergslandSearch for articles by this author , Alan P. VenookxAlan P. VenookSearch for articles by this author Show More University of California, San Francisco, CA https://doi.org/10.1200/JCO.2002.20.9.2220 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis
Authors: William J. Sandborn, Brian G. Feagan, Douglas C. Wolf, Geert D’Haens, Severine Vermeire, Stephen B. Hanauer, Subrata Ghosh, Heather Smith, Matthew Cravets, Paul A. Frohna, Richard Aranda, Sheila Gujrathi, Allan Olson
Journal: New England Journal of Medicine (2016)

Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.
Vorinostat (SAHA) Combined With High-Dose Gemcitabine/Busulfan/Melphalan (SAHA/Gem/Bu/Mel) With Autologous Stem-Cell Transplant (ASCT) In Patients With Refractory Lymphomas
Authors: Yago Nieto, Peter F Thall, Benigno C. Valdez, Chitra M Hosing, Sairah Ahmed, Roy B Jones, Nina Shah, Paolo Anderlini, Muzaffar H. Qazilbash, Uday R Popat, Qaiser Bashir, Elizabeth J Shpall, Amin Alousi, Partow Kebriaei, Patricia Fox, Rolland Bassett, Christina Chancoco, Yasuhiro Oki, Michelle A. Fanale, Nathan Fowler, Frederick Hagemeister, Jorge E Romaguera, Richard E Champlin, Borje S. Andersson
Journal: Blood (2013)
Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells
Authors: Cynthia M Fehres, Sanne Duinkerken, Sven CM Bruijns, Hakan Kalay, Sandra J van Vliet, Martino Ambrosini, Tanja D de Gruijl, Wendy WJ Unger, Juan J Garcia-Vallejo, Yvette van Kooyk
Journal: Cellular and Molecular Immunology (2015)
Three or Six Months of Adjuvant Chemotherapy for Colon Cancer: Compliance and Safety of the Phase III Italian Tosca Trial
Authors: S. Lonardi, R. Labianca, G. Rosati, M. Di Bartolomeo, L. Gianni, N. Pella, B. Massidda, C. Boni, M.G. Zampino, F. Pasini, P. Marchetti, M. Cantore, A. Santoro, L. Ciuffreda, D. Ferrari, A. Zaniboni, V. Montesarchio, E. Maiello, I.C. Floriani, A. Sobrero
Journal: Annals of Oncology (2014)
Sundays at Seven
Authors: Leslie G. Cohen
Journal: Annals of Internal Medicine (2016)

On Being a Doctor3 May 2016Sundays at SevenLeslie G. Cohen, MDLeslie G. Cohen, MDFrom Chestnut Hill, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2447 Audio Reading - “Sundays at Seven” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Sundays at Seven," by L.G. Cohen. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail While rummaging through a cellar closet, I noticed an unmarked, dust-covered cardboard box. To my surprise it was full of audio cassettes; my collection of now-obsolete radio tapes of “The Jack Benny Show” and other well-known comedians of that era. I could never bear to throw them away. Just seeing them again made me chuckle and brought back a memory from childhood. Like many families on Sunday nights after dinner, before television eclipsed radio, we listened to these programs.I thought about my favorite program, “The Jack Benny Show,” and could still hum his theme songs. As I thumbed through ... Author, Article, and Disclosure InformationAffiliations: From Chestnut Hill, Massachusetts.Corresponding Author: Leslie G. Cohen, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Sundays at Seven” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Sundays at Seven," by L.G. Cohen. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 3 May 2016Volume 164, Issue 9Page: 629-630KeywordsEatingElderlyForecastingHearingMemoryNursing homesParalysisStrokeThoraxWheelchairs ePublished: 3 May 2016 Issue Published: 3 May 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Simultaneous profiling of transcriptome and DNA methylome from a single cell
Authors: Youjin Hu, Kevin Huang, Qin An, Guizhen Du, Ganlu Hu, Jinfeng Xue, Xianmin Zhu, Cun-Yu Wang, Zhigang Xue, Guoping Fan
Journal: Genome biology (2016)

Single-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear. Here, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression. Our method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation.
Neuroendocrine interrelationships in major depressive disorder
Authors: S D Targum, A C Sullivan, S M Byrnes
Journal: American Journal of Psychiatry (1982)

The authors administered the thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) to 54 patients who met DSM-III criteria for major depressive disorder and to 19 nondepressed patients. A blunted thyrotropin (TSH) response to TRH injection was noted in 18 depressed patients (33%) but in no nondepressed patients. An escape from dexamethasone suppression was noted in 23 depressed patients (43%) but in only 2 nondepressed patients (11%). The combined sensitivity of the DST and the TRH test in identifying major depressive disorder was 67% with 92% specificity. Only 6 depressed patients (11%) had abnormal responses to both the DST and the TRH test, suggesting that the hypothalamic-pituitary-adrenal axis dysregulation and hypothalamic-pituitary-thyroid axis dysregulation are independent phenomena. These findings support the combined use of these neuroendocrine tests in clinical practice.
A rapid immunoassay to determine concentrations of busulfan in plasma
Authors: S. J. Salamone, J. Courtney, R. Harney, S. He, G. Lundell
Journal: Journal of Clinical Oncology (2007)

7111 Background: High-dose busulfan is an important component of many bone marrow transplantation preparative regimens. High busulfan plasma levels have been shown to increase the chance of veno-occlusive disease and low levels are associated with recurrence of disease or graph rejection. Currently, busulfan levels are monitored by physical methods which are expensive and time- consuming, resulting in relatively low overall use of busulfan testing for dose adjustment. Methods: Novel, highly selective antibodies for busulfan have been generated and micro-titer plate immunoassays that are capable of quantifying busulfan levels in plasma have been developed. The assay was configured using a busulfan-horseradish peroxidase conjugate as the reporter group and busulfan monoclonal antibodies. The assay requires only 5 μL of plasma per determination with no sample preparation. Results: The immunoassay has a standard curve based on busulfan with a range of 75 to 2,000 ng/mL. The time to first result is 30 minutes with up to 240 tests generated per hour. The coefficient of variation (CV) on signal is &lt; 5% for an entire plate and the 95% confidence interval for negative samples (n=78) is below the lowest calibrator of 75 ng/mL. Cross-reactivity with the major inactive metabolites (tetrahydrothiophene,tetramethyl sulfone and tetrahydrothiophene-3-ol-1,1-dioxide), are &lt;0.1%. Clinical samples (n=70) correlate well to LC-MSMS or GC-MS (R &gt; 0.97) with a slope of &lt; 1.05. Conclusions: This immunoassay method may be suitable for determining levels of busulfan in human plasma. It offers the advantages of using a smaller sample size, does not require sample preparation and is less labor intensive than other methods. The ability to make 240 determinations per hour enables effective routine monitoring of busulfan levels in clinical practice. No significant financial relationships to disclose.
Use of a nanoparticle-based artificial olfactory system, NaNose, to distinguish malignant from benign pulmonary nodules.
Authors: N. Peled, M. Hakim, H. Haick, P. A. Bunn, Y. E. Miller, T. C. Kennedy, J. D. Mitchell, M. J. Weyant, F. R. Hirsch
Journal: Journal of Clinical Oncology (2010)

10521 Background: There is no approved screening method for lung cancer and CT scanning has a high rate of false positives. Exhaled breath analysis for volatile organic compounds (VOCs) has the potential to distinguish between benign and malignant nodules. Recently, we showed that novel gold (Au) nanoparticles-based Artificial Olfactory System; NaNose, distinguishes between malignant (non-small lung cancer; NSCLC) and non-malignant human breaths and cell lines. In this study we incorporated the NaNose in our pulmonary “nodule clinics” where patients are evaluated for a suspicious lung nodule. Methods: 34 patients with lung nodules and 21 healthy subjects were tested for exhaled breath VOC profile. Patients were further evaluated as clinically appropriate. The exhaled breath was sampled by Eco Medics collecting system and the air passed through a Tenax SKC tube, which was analyzed for: (i) gas-chromatography/mass- spectrometry (GCMS) combined with solid phase micro-extraction (SPME) for determining the chemical nature of the VOCs; and by (ii) NaNose (Technion, Haifa Israel), for obtaining simple, real-time discriminations between the samples. For the latter, the electrical properties of the sensors were measured by a programmed time-related analyzer. Samples from healthy subjects were used to standardize the signals. Results: 25 patients had a malignant nodule (23 NSCLC; 12 adenocarcinomas, 8 squamous cell carcinomas, 3 undifferentiated and 2 SCLC) and 9 had benign nodules. Smoking history, comorbidity and nodule location were not different between the groups. Principle component analysis of the nanoparticle-based sensors yielded a significant discrimination between the malignant and the benign nodules (p < 0.007; sensitivity 88%; specificity 90%). The SPME/GCMS analysis identified 1000 different VOCs, but forward stepwise discrimination analysis produced different VOCs profile for the groups. VOCs that did not overlap between the malignant and the benign groups were isolated and selected as “malignant lung nodule” biomarkers. Conclusions: Non-invasive, exhaled breath analysis using the NaNose for VOCs profile discriminates between malignant and benign pulmonary nodules. No significant financial relationships to disclose.
Synthesis of Human Placental Alkaline Phosphatase in Vitro by the ChaGo Cell Line2
Authors: Marilyn A. Ludueña, Howard H. Sussman, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1974)

Human placental alkaline phosphatase was purified from an epithelial cell line which also synthesizes chorionic gonadotropin in vitro. The ChaGo alkaline phosphatase was immunochemically, biochemically, and functionally very similar to the alkaline phosphatase synthesized by the original tumor tissue and by normal placentas
PWE-335 Colorectal cancer outcomes: what about the also-rans?
Authors: JRW Hall, JG Williams
Journal: Gut (2015)

<h3>Introduction</h3> Despite advances in non-surgical oncological treatments, surgical resection of the primary tumour is still required to “cure” a patient of colorectal cancer (CRC). Surgeon specific outcome reporting in colorectal cancer surgery focuses on patients who undergo major elective resection, raising a concern that only data for “low risk” patients are included, thus giving an incomplete picture of a Unit’s overall performance in the management of colorectal cancer. The aim of this study was to analyse the frequency, reasons and outcomes of patients who do not undergo resection. <h3>Method</h3> Details of 1093 patients diagnosed with CRC in a single institution between April 2008 and April 2013 were recorded prospectively. Analysis of demographics, staging, treatment, reasons for non-surgical management and survival was performed. Patients who underwent local tumour resection were excluded (n = 40). <h3>Results</h3> 827 (75.6%) patients underwent primary major resection of their tumour, of which 62 patients were stage IV at the time of surgery. 226 (24.4%) patients were treated non-operatively. Of these patients, 143 (63.2%) had Stage IV cancer (37 (25.9%) underwent palliative surgery). 44(19.5%) patients were deemed unfit for surgery, 2 (0.9%) had complete response to chemo-radiotherapy and 23(10.2%) patients declined surgical intervention. During follow up (median 32 months, range 0–78 months), 253 (30.6%) patients who underwent a major resection died, with 175 deaths (69.2%) directly attributed to cancer. For the non-resection group, 182 (68.4%) patients died, with 137 deaths (75.3%) due to cancer. Median survival for patients undergoing major resection was 45 months: 729 (88.1%) and 667 (80.7%) patients were alive at 12 and 24 months respectively. Median survival for non-resection patients was 4 months, with 108 (48.2%) and 84 (37.5%) patients alive at 12 and 24 months respectively, p &lt; 0.0001 (Mann-Whitney U test). Median survival following surgical intervention for Stage IV disease was similar for major resection (12 months) or a palliative procedure (8 months). During the 5 year period studied, the rate of non-resection remained constant at 22.7%, 21.9%, 22.9%, 22.8% and 24.5% year on year respectively, indicating that there was no change is selection criteria for major resection. <h3>Conclusion</h3> To give a complete picture of a unit’s performance for colorectal cancer treatment, data on the rate of non-resection of CRC, together with an analysis of reasons for non-resection should be included in annual Unit or surgeon-specific outcome reports,. Major resection for Stage IV disease does not appear to offer any survival advantage over lesser, palliative procedures. <h3>Disclosure of interest</h3> None Declared.
Abstract 349: Gastrin and D1 Dopamine Receptor Interact to Induce Natriuresis and Diuresis
Authors: Yue Chen, Laureano D. Asico, Shuo Zheng, Van Anthony M. Villar, Duofen He, Lin Zhou, Chunyu Zeng, Pedro A. Jose
Journal: Circulation Research (2014)

Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto (WKY) rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (CCK B R; CI-988) or D 1 -like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D 1 -like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats (SHRs). The gastrin/D 1 -like receptor interaction was also confirmed in RPT cells. In RPT cells from WKY but not SHRs, stimulation of either D 1 -like or gastrin receptor inhibited Na + -K + -ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from WKY and SHRs, CCK B R and D 1 receptor (D 1 R) co-immunoprecipitated, which was increased after stimulation of either D 1 R or CCK B R in RPT cells from WKY rats; stimulation of one receptor increased RPT cell membrane expression of the other receptor, effects that were not observed in SHRs. These data suggest that there is a synergism between CCK B R and D 1 -like receptors to increase sodium excretion. An aberrant interaction between the renal CCK B R and D 1 -like receptors (e.g., D 1 R) may play a role in the pathogenesis of hypertension.
Comparison of metabolic activity in mantle cell lymphoma at biospy site and other tumor sites using 18F-FDG PET
Authors: S. Chundru, M. Nguyen, I. Jaiyesimi, O. Wong, V. Douglas-Nikitin, L. Nadeau, H. Balon, N. Mardis, D. Fink-Bennett
Journal: Journal of Clinical Oncology (2007)

18529 Background: Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin’s lymphoma (NHL) with a variable clinical course ranging from indolent to aggressive. Treatment for MCL is complicated by this variability, as systemic chemotherapy for NHL is directed by the aggressiveness of the lymphoma. Previous attempts have been made to correlate clinical outcome in MCL with histologic features. More recently, measurement of metabolic activity using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) was found to be highly correlative with the aggressiveness of NHL. Given the clinical heterogeneity of MCL, the search for the true metabolic status in MCL is important in prognostication and management. We propose to study the metabolic activity in MCL by comparing the maximum SUV at the site of biopsy with the highest SUV in other MCL areas of the body. Methods: 12 patients with newly diagnosed MCL and having staging by FDG-PET were identified. PET(CT) body scans were obtained in the usual fashion. The SUVs, defined as tumor activity divided by dose injected per lean body mass, from the PET and PET-CT cameras were cross validated to produce the same value in a given phantom and patient. Maximum biopsy SUV was measured by searching the maximum value within a volume of interest over the known biopsy site, and highest body SUV was similarly searched in known tumor sites in other body areas. Results: One patient was excluded because the tumor at the biopsy site had been completely resected. The remaining 11 patients (M:F=8:3, age=63±8 yrs) were analyzed. The SUV at biopsy sites ranged from 2.1 to 9.8 (mean=5.2±2.3). The SUV in other tumor sites ranged from 4.8 to 18.6 (mean=8.9±4.1), which was significantly higher when compared to the respective biopsy site (p=0.0036). Conclusions: As the SUV of MCL at the biopsy site may not represent the highest SUV, it is important to search other tumor sites in the body for the highest SUV to help in grading, managing, and subsequent monitoring of MCL. Perhaps FDG-PET can direct biopsies to tumor sites with the highest SUV and subsequently provide useful histologic detail for predicting clinical course. Future study is needed to correlate the maximal SUV of MCL with histology and clinical course. No significant financial relationships to disclose.