tbuckley/cabot-search huggingface dataset:
Different Distribution of 62Cu ATSM and 18F-FDG in Head and Neck Cancers
Authors: Arpakorn Kositwattanarerk, Myungmi Oh, Takashi Kudo, Yasushi Kiyono, Tetsuya Mori, Yuichi Kimura, Rikiya Maruyama, Yasuhisa Fujibayashi, Shigeharu Fujieda, Hidehiko Okazawa
Journal: Clinical Nuclear Medicine (2012)

Purpose: [62Cu]-diacetyl-bis(N4-methlythiosemicarbazone) (Cu-ATSM) was used to delineate hypoxic tissue in head-and-neck cancer, and its distribution was compared with that of 18F-FDG. Materials and Methods: Thirty patients with head-and-neck cancer underwent Cu-ATSM and FDG PET within a 1 week interval. Accumulation of tracer for each PET image was converted to SUV. After coregisteration of PET images with individual anatomic images, multiple small ROIs were drawn on the tumor mass and applied to both PET images. SUV values were obtained for all ROIs (SUVroi), and the SUVroi regression lines between Cu-ATSM and FDG of each tumor were determined. Results: The SUV mean of Cu-ATSM was lower than that of FDG for both squamous cell carcinoma (SCC) and adenocarcinoma (P < 0.05). In 27 patients with SCC, Cu-ATSM accumulated higher in the peripheral region than in the center of the tumor, and FDG showed the other tendency. Thus, the relationship of the SUVroi for Cu-ATSM and FDG showed a negative correlation in SCC. However, 3 adenocarcinoma cases showed similar and homogenous accumulation in the tumor mass with a positive SUVroi correlation for the 2 tracers. The regression slope means were −0.12 ± 0.08 for SCC (n = 27) and 0.28 ± 0.12 (n = 3) for adenocarcinoma. Conclusion: In patients with head-and-neck cancer, intratumoral distribution of Cu-ATSM and FDG showed a negative correlation in SCC and a positive correlation in adenocarcinoma. The 2 tracers represented different pathophysiological microenvironments in different tumors, suggesting that noninvasive hypoxic tissue imaging with Cu-ATSM would be beneficial in the pretreatment evaluation of head-and-neck cancer.
Induction of Subacute Skeletal Fluorosis in a Case of Multiple Myeloma
Authors: Phin Cohen, Frank H. Gardner
Journal: New England Journal of Medicine (1964)

THE morbidity in multiple myeloma is chiefly related to four complications: anemia; susceptibility to infections; renal failure; and pathologic fractures and incapacitating, demoralizing bone pain.1 The use of chemotherapy in myeloma has not been as salutary as its application to chronic lymphocytic leukemia. Ethyl carbamate, glucocorticoids, cyclophosphamide and more, recently, phenylalanine mustards have been used with varying degrees of success in the hands of different groups of investigators. Although anemia and bone pain have been ameliorated in many cases in which any one of these drugs have been given, none achieve the therapeutic effectiveness of nitrogen mustard derivatives in the . . .
MISMATCH BETWEEN BRAIN NATRIURETIC PEPTIDE LEVELS AND FLUID CONGESTION STATUS ASSESSED USING MULTI-FREQUENCY BIO-IMPEDANCE ANALYSIS IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Fumie Otomo, Mitsuaki Endo, Eiichi Akiyama, Yasushi Matsuzawa, Masaaki Konishi, Toru Suzuki, Sae Saigo, Jin Kirigaya, Hidefumi Nakahashi, Mitsuho Inoue, Makoto Shimizu, Hideo Himeno, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2015)
PTU-165 Worldwide Epidemiological Evidence Supports A Common Factor Predisposing To Non-cardia Gastric Cancer And Protecting From Oesophageal Adenocarcinoma
Authors: MH Derakhshan, DH Brewster, JJ Going, EV Robertson, M Arnold, D Forman, KE McColl
Journal: Gut (2014)

<h3>Introduction</h3> During last three decades, global incidence of oesophageal adenocarcinoma has increased more rapidly than any other cancer. A concurrent reduction in the incidence of gastric cancer has been reported from some populations. We aimed to examine the geographical pattern of oesophageal adenocarcinoma versus gastric non-cardia cancer across the world where reliable cancer registry data were available. <h3>Methods</h3> Data were abstracted from “Cancer Incidence in Five Continents” Volume 10. Oesophageal and gastric cancers were selected based on ICD-10 codes C15 and C16, respectively. Oesophageal adenocarcinomas were identified by ICD-O morphology codes. Datasets reporting &gt;500 cases for total gastric cancer and &gt;100 for total oesophageal cancer were selected. We examined correlation between age-standardised Incidence rates (ASR) of oesophageal adenocarcinoma and non-cardia gastric cancer using Spearman’s non-parametric correlation coefficient (CC). We also allocated cardia cancers into oesophageal and non-cardia gastric adenocarcinoma categories based on gender ratio for oesophageal adenocarcinoma and non-cardia gastric cancer in each dataset. <h3>Results</h3> Out of 424 datasets from 290 cancer registries, 206 datasets covering 40 countries met the selection criteria. There was a strong inverse correlation between oesophageal adenocarcinoma and gastric non-cardia cancer in males (CC= –0.768, p &lt; 0.001) and females (CC = –0.705, p &lt; 0.001). After dividing cardia cancer into two subtypes with potentially oesophageal or gastric origin and adding them to original oesophageal adenocarcinoma or gastric non-cardia groups, the inverse correlation remained strong in males (CC= –0.660, p &lt; 0.001) and females (CC= –0.536, p &lt; 0.001). Oesophageal adenocarcinoma only showed a rise when incidence of non-cardia gastric cancer fell below 9/100,000 person-years for males and 4.5/100,000 person-years for females. <h3>Conclusion</h3> This cross-sectional study is consistent with a common underlying factor predisposing to non-cardia gastric cancer and protecting from oesophageal adenocarcinoma, such as H. pylori atrophic gastritis. If this is the case, then the incidence of non-cardia gastric cancer would need to fall to substantially lower levels than currently seen in Far Eastern populations before any rise in oesophageal adenocarcinoma would be apparent. <h3>Disclosure of Interest</h3> None Declared.
Alkali-Resistant Hemoglobin in Aplastic Anemia of Both Acquired and Congenital Types
Authors: Nasrollah T. Shahidi, Park S. Gerald, Louis K. Diamond
Journal: New England Journal of Medicine (1962)

DURING a study of patients with aplastic anemia1 it was noted that blood from such patients showed an increased amount of alkali-resistant hemoglobin. It is known that increased production of alkali-resistant or fetal hemoglobin is usually associated with some genetically determined anemias such as thalassemia and sickle-cell anemia. Scattered reports have also indicated that production of fetal hemoglobin may be reactivated in some acquired disorders such as pernicious anemia, multiple myeloma,2 molar pregnancy3 and aplastic anemia.2 , 4 , 5 The evaluation of alkali-resistant hemoglobin in this last condition, however, has yielded conflicting results. Although some investigators have found abnormal amounts of this hemoglobin . . .
Mitral Annular Calcification
Authors: Thorsten Klink, Johannes T Heverhagen
Journal: New England Journal of Medicine (2015)

An 81-year-old woman had cardiac failure after surgery for oral cancer. A diagnostic workup indicated perioperative overhydration and pulmonary embolism, and chest radiography revealed a large, dense area of calcification overlying the heart, consistent with mitral annular calcification.
QUANTITATIVE EVALUATION OF SERIAL BONE SCANS FOR ASSESSING THERAPEUTIC RESPONSE AND RADIOGRAPHIC CORRELATION IN BONY METASTASIS OF BREAST CANCER.
Authors: Carlos Gutierrez, Edmund E. Kim, Thomas P. Haynie
Journal: Clinical Nuclear Medicine (1983)

Division of Nuclear Radiology, University of Texas Medical School at Houston, and Section of Nuclear Medicine, M.D. Anderson Hospital, Houston, Texas.
Abstract P4-04-01: Proliferation, Migration, Stem Cell Activity and the Role of Cyclin D1 in Breast Cancer
Authors: RM Lamb, S Lehn, N Tobin, P Berglund, G. Landberg
Journal: Cancer Research (2010)

Abstract Background: Proliferation, migration, and stem cell (SC) activity have all been implicated in the development and progression of breast cancer. Growing evidence suggests a relationship between these cellular characteristics, which are tightly regulated by complex signalling pathways. The oncogene cyclin D1 is an essential cell cycle protein that regulates G1 to S phase transition and is overexpressed in many breast cancers. Despite the proliferation activating properties of cyclin D1 it has been linked to a less malignant phenotype. Aim: The aim is to investigate the relationship between migration, proliferation and SC activity in breast cancer and to determine the molecular mechanisms that control these processes focusing on cyclin D1. Methods and Results: To establish a link between proliferation and migration two breast cancer cell lines (MDAMB231 and MDAMB468) were quiesced and proliferation assessed by Ki67 and migration by transwell migration assays. G0/G1 cells displayed an increased migratory capacity (2.9 ±0.15 fold) compared to cycling cells. Next we downregulated cyclin D1 in actively cycling cells using siRNA which resulted in significantly decreased proliferation and the novel observation of increased migration (1.7±0. 19 fold). Having established a link between proliferation and migration the next aim was to investigate relationships with SC activity. To achieve this, cells were sorted following Hoechst 33342 and 7AAD labelling into three populations G0/G1, S, and G2/M. SC-like activity was assessed using a non-adherent mammosphere culture system where single cells are seeded at a density of 500 cells per cm2 for cultured for 7 days. The data clearly demonstrated that G0/G1 cells had increased migratory capacity and also SC-like activity (1.5±0.2 fold) compared to actively cycling cells. Interestingly, down-regulation of cyclin D1 increased both migratory and SC-like activity with most significant effects observed in G0/G1 and S phase of the cell cycle indicating that cyclin D1 is a key protein in the regulation of these cellular processes. When downregulating the cyclin D1 associated kinases CDK4/6 no effect on migration or SC activity was observed suggesting that cyclin D1 affects these cellular processes independent of CDK activation. Finally, when analysing a large set of premenopausal breast cancers we observed an inverse, proliferation-independent link between cyclin D1 and cancer recurrence as well as tumour size (p=0.03), validating that the protein might abrogate infiltrative and malignant behaviour in vivo. Conclusion: These novel functions of cyclin D1 illustrates the interplay between tumor proliferation and migration and SC activity and may explain the lessened malignant behaviour in cyclin D1 high breast cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-01.
Abstract 364: Exercise slows tumor progression and normalizes tumor vasculature in murine models of breast cancer.
Authors: Allison S. Betof, Lee W. Jones, Mark W. Dewhirst
Journal: Cancer Research (2013)

Abstract The effect of endurance exercise to improve post-ischemia perfusion of normal tissues is established but whether such effects extend to hypoxic solid tumors is largely uninvestigated. Thus, we evaluated the hypothesis that exercise slows tumor growth and improves the structure and function of tumor blood vessels, resulting in decreased hypoxia and increased effectiveness of cyclophosphamide chemotherapy. To investigate the effects of exercise on tumor microenvironment, we utilized voluntary wheel running after tumor cell implantation in two orthotopic models of murine breast cancer: ER(-) 4T1 breast tumor cells in BALB/c mice and ER(+) E0771 breast tumor cells in C57Bl/6 mice. Endurance exercise significantly increased microvessel density (CD31, p&amp;lt;0.003), vessel maturity (co-localization of NG2 and desmin with CD31, p&amp;lt;0.003), and perfusion (ADCperf, p&amp;lt;0.05), which resulted in significant reductions in intratumoral hypoxia (EF5, p&amp;lt;0.002). This was associated with significant inhibition of tumor growth (p&amp;lt;0.004), and increased apoptosis compared with sedentary controls (cleaved caspase-3, p&amp;lt;0.05). Next, given that hypoxia is a major cause of chemoresistance, we tested whether exercise-induced improvements in perfusion and reduction of hypoxia could improve the efficacy of conventional chemotherapy. The combination of exercise plus cyclophosphamide was associated with significantly prolonged growth delay compared with exercise or chemotherapy alone (p&amp;lt;0.01). In this work, we provide the first conclusive evidence that exercise may do more than decrease symptoms and improve quality of life for cancer patients. Our data suggest that exercise may be an effective adjunct therapy to reduce tumor hypoxia leading to enhanced efficacy of anticancer therapy. Funding: ASB is supported by DOD BC093532. LWJ is supported by NIH CA143254, CA142566, CA138634, CA133895 and funds from George and Susan Beischer. MWD is supported by NIH CA40355. Citation Format: Allison S. Betof, Lee W. Jones, Mark W. Dewhirst. Exercise slows tumor progression and normalizes tumor vasculature in murine models of breast cancer. [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 364. doi:10.1158/1538-7445.AM2013-364
806 ISG15 SUPPRESSION IN HEPATOCYTES, MEDIATED BY LNP01-FORMULATED SIRNAS, LEADS TO ENHANCED RESPONSIVENESS TO INTERFERON IN VIVO
Authors: C.I. Real, R. Broering, K. Jahn-Hofmann, L. Ickenstein, M. John, K. Kleinehr, G. Gerken, J.F. Schlaak
Journal: Journal of Hepatology (2012)
Expanded coverage under US health act projected to cost $104bn less than expected
Authors: M. McCarthy
Journal: BMJ (2014)

The cost of expanding health insurance coverage through the US health reform law, the Affordable Care Act, will cost $104bn (£62bn; €75bn) less than expected over the next decade, according to a new report.1

The report, which was prepared by the Congressional Budget Office and Joint Commission on Taxation, which are non-partisan congressional agencies, projects that the cost of health coverage provisions of the 2010 health reform law will have a net cost of $36bn for 2014, $5bn less than the agencies had projected previously, and a net cost of $1383bn for the 2014-15 period, $104bn less than previously projected.

The lower costs in 2014 were largely because of lower than expected premiums for plans offered on …
A1.20 HDAC5 regulates CXCL chemokine expression in RA FLS via the transcription factor IRF1
Authors: C Angiolilli, A M Grabiec, B S Ferguson, B Malvar Fernandez, P P Tak, T McKinsey, D L Baeten, K A Reedquist
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> HDAC inhibitors (HDACi) display anti-inflammatory properties in animal and in vitro models of rheumatoid arthritis (RA), as well as initial safety and efficacy in the treatment of systemic onset juvenile idiopathic arthritis. However, most currently available HDACi display relatively little selectivity for class I (HDAC 1-3, 8) and class II (HDAC 4-7, 9, 10) HDACs, let alone individual HDACs. The present study aims to better characterise the different contributions of HDAC family members to the inflammatory activation of RA fibroblast-like synoviocytes (FLS). <h3>Materials and Methods</h3> HDAC mRNA expression in RA FLS was measured by quantitative PCR, and the activity of class I, IIa and IIb HDACs was assessed by enzymatic assays. FLS were either transduced with adenoviral GFP-HDAC5 or transfected with HDAC5 siRNA, and gene expression was analysed by qPCR array, while chemokine production was measured by ELISA. Analysis of transcription factors was performed using DNA-binding and ELISA-based assays. <h3>Results</h3> Class IIa HDAC5 mRNA expression, but not class IIa HDAC activity, was significantly and selectively reduced after RA FLS stimulation with TNFα and IL-1β. Mimicking of HDAC5 downregulation by use of siRNA, and adenoviral overexpression of HDAC5, demonstrated that of 84 inflammation-related gene products, HDAC5 downregulation was sufficient and required to allow optimal expression of IFN-B, CXCL9, CXCL10, and CXCL11. Promoter analysis of these genes compared to non-regulated genes indicated a significant enrichment in this gene set for NF-KB, STAT1 and IRF1 binding sites. Silencing of HDAC5 expression had no effect on DNA-binding activity of MEF2 transcription factors, the best described targets of class IIa HDACs, nor NF-KB or STAT1. However, HDAC5-silencing significantly enhanced IL-1β-dependent nuclear accumulation of IRF1. <h3>Conclusions</h3> Our results show that mRNA expression and activity of distinct HDAC members in RA FLS are regulated in a different fashion by inflammatory stimuli. Silencing of class IIa HDAC5 increases CXCL chemokine production, associated with enhanced nuclear accumulation of IRF1, a transcription factor required for induction of these genes. Our results suggest that the design of HDACi targeting specific HDACs can be used to selectively modulate inflammatory gene expression in RA.
“T-U-P” Syndrome, or Pseudoatrial Flutter
Authors: Gregory M Marcus, J Edwin Atwood
Journal: New England Journal of Medicine (2003)

77-year-old man with a remote history of atrial fibrillation presented to the emergency department reporting fatigue and weakness. The patient said he had not made any recent changes in his diet and that he did not have nausea, vomiting, or diarrhea. He also said he had no palpitations or sensations of a rapid heart rate. He was not taking any atrioventricular nodal blocking agents. An electrocardiogram was obtained, and an atrial flutter with a conduction ratio of 4:1 was diagnosed (Panel A). Laboratory values were remarkable only for a serum potassium level of 2.8 mmol per liter. One month before this visit, the patient had begun to receive 25 mg of hydrochlorothiazide daily for hypertension. After the electrocardiogram was obtained, potassium supplementation was prescribed, and treatment with the diuretic medication was discontinued. Repeated electrocardiography demonstrated sinus rhythm (Panel B). The pseudoatrial flutter, or “T-U-P” syndrome, as seen in Panel A, with small T waves (large arrow), followed by U waves (asterisk), followed by P waves (small arrow), with first-degree atrioventricular block, was attributed to the presence of hypokalemia as a result of the hydrochlorothiazide therapy. In Panel B, the T waves (large arrow) and P waves (small arrow) are shown. Copyright © 2003 Massachusetts Medical Society. a 150 Hz 25 mm/sec 10 mm/mV
Bone Marrow Transplants Used Against Advanced Breast Cancer
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Bone Marrow Transplants Used Against Advanced Breast Cancer Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 18, 20 September 1989, Pages 1352–1353, https://doi.org/10.1093/jnci/81.18.1352 Published: 20 September 1989
P180 The Importance Of Accurate Pre-operative Biopsy In The Radical Management Of Mesothelioma - Don't Blame The Physician Just Keep Taking More Bites
Authors: A. Sharkey, R. Vaja, V. Joshi, J. L. Quesne, S. Muller, A. Nakas, C. Richards, D. Waller
Journal: Thorax (2014)

<h3>Introduction</h3> Histological subtype is an independent prognostic factor in malignant pleural mesothelioma (MPM). Accurate typing is required to offer appropriate therapy, with surgery generally being reserved for epithelioid disease due to the poor survival in biphasic and sarcomatoid MPM. Preoperative tissue can be obtained by a variety of methods which may yield suboptimal specimens. We aimed to investigate whether the mode of biopsy influenced the accuracy of diagnosis. <h3>Methods</h3> We reviewed clinicopathological data from all patients who underwent radical surgery for MPM from 2000–2014, and compared subtyping from biopsies and resection specimens. In addition, a subspecialty expert consultant histopathologist reviewed biopsies from all biphasic cases. <h3>Results</h3> In total, 335 patients had available pathological data available. 61(18.2%) showed discordance in subtyping between the diagnostic biopsy and the resection specimen. In 53 patients a poorer prognosis cell type was identified at resection (see Table). There was poorer survival in the discordant group; median survival 8.2 vs 15.2 month (p = 0.001 HR=1.659 95% CI 1.227–2.243). Discordance was found to be an independent predictor of survival on multivariate analysis (HR 1.653 95% CI 1.207–2.264 p = 0.002). There was no effect of method of pre-operative biopsy on concordance (p = 0.306). There was also no difference in the accuracy of the diagnosis if a surgical biopsy was performed versus medical thoracoscopy or a radiologically guided biopsy (p = 0.768). In 26 (18.4%) cases there was discordance between pre-operative biopsy and post-operative histological subtype. In 22 patients a poorer prognosis cell type was identified. <h3>Conclusion</h3> These data demonstrate potential inaccuracy of current biopsy practice with accompanying impaired patient outcome. This correlates with our existing knowledge of the heterogeneity of MPM and the difficulty of subtyping from small biopsies. A wide distribution of biopsy sites within the hemithorax is likely to be more significant in obtaining an accurate histological diagnosis than the mode of biopsy itself.
The Natural History of Cirrhosis
Authors: Arthur J. Garceau, Thomas C. Chalmers
Journal: New England Journal of Medicine (1963)

THE purpose of this report is to characterize a large group of patients with cirrhosis and esophageal varices and to determine their survival by means of a prospective survey. Such a survey is of interest in itself, and can supply background information useful for the design of clinical trials. The study consists of the analysis of data collected on 471 patients with unequivocal esophageal varices seen by members of the Boston Inter-Hospital Liver Group§ at the associated hospitals in the years 1959–1961. By comparison with previously published data the influence of recent advances in therapy upon survival may become apparent. . . .