tbuckley/cabot-search huggingface dataset:
Abstract 3365: Aldolase A induces invasion/metastasis of lung cancer through modulating HIF1-α and is a marker for poor clinical outcome
Authors: Yu-Chan Chang
Journal: Cancer Research (2014)

Abstract The dysregulated metabolism is an emerging hallmark of cancer. However, little is known about the metabolic requirements during cancer progression. Therefore, identifying metabolic genes that are critical for supporting cancer invasion/metastasis may provide novel targets for cancer diagnosis and therapy. By analyzing gene expression and proteomic profile of invasive lung cancer cells CL1-5 and its parental counterpart CL1-0, we identified Aldolase A (ALDOA), an enzyme of glycolysis pathway, is overexpressed in CL1-5 and is significantly associated with disease recurrence in lung cancer patient microarray datasets. Moreover, HIF-1α was identified as the most significant transcription factor in ALDOA-recurrence gene signature by IPA upstream regulator analysis. Furthermore, Immunohistochemistry analysis confirmed the expression of ALDOA was markedly higher in lung cancer tumors than in normal lung. High ALDOA expression was found significantly associated with lymph node involvement and disease recurrence. Moreover, overexpression of ALDOA was significantly associated with poor outcome in both overall and disease-free survival. Knockdown of ALDOA expression was found to suppress invasion potentials in highly invasive lung cancer cell lines while complementary overexpression of ALDOA in poorly invasive cells promoted it in vitro and in vivo. ALDOA overexpression also accelerated glucose consumption, ATP utilization and lactate production. Knockdown of ALDOA expression in CL1-5 abolished HIF-1α expression with concurrent Mesenchymal-to-Epithelial Transition (MET). Moreover, IHC analysis shows an inverse correlation between ALDOA and E-cadherin and combination of high ALDOA and low E-Cadherin showed an unfavorable outcome, in a sharp contrast, compared to patients with low ALDOA and high E-cadherin. Here, we identified ALDOA as a critical glycolytic enzyme involved in lung cancer progression and may be a marker for poor clinical outcome. Citation Format: Yu-Chan Chang. Aldolase A induces invasion/metastasis of lung cancer through modulating HIF1-α and is a marker for poor clinical outcome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3365. doi:10.1158/1538-7445.AM2014-3365
Optimization of a synthetic β-catenin-dependent promoter for tumor-specific cancer gene therapy
Authors: Kai S. Lipinski, Hakim A. Djeha, Jonathan Gawn, Suzanne Cliffe, Norman J. Maitland, Daniel H. Palmer, Andrew Mountain, Alistair S. Irvine, Christopher J. Wrighton
Journal: Molecular Therapy (2004)

We recently published the construction and evaluation of a beta-catenin-dependent, highly active promoter, CTP1, and its possible application for the treatment of colorectal cancer using gene-directed enzyme prodrug therapy with adenoviral (Ad) vectors. Alternative Ad-based approaches such as tumor-specific, replication-competent vectors and/or exploiting therapeutic gene products with intrinsic toxic activity, such as gibbon ape leukemia virus fusogenic membrane glycoprotein, diphtheria toxin A (DTA), and ricin, would demand a very tightly regulated promoter to avoid breakthrough replication and toxicity in nontumor tissue and Ad producer cell lines. In this study we optimized the activity/specificity profile of the synthetic beta-catenin-dependent promoter by varying its basal promoter, the number of Tcf binding sites, and the distance between these and the basal promoter. The optimal promoter, CTP4, showed virtually undetectable expression in cells with normal beta-catenin regulation but high level expression in cells deregulated for beta-catenin. Using CTP4 we were able to generate, for the first time to our knowledge, an Ad vector expressing fully active wild-type DTA without the need for time-consuming and cumbersome production systems. CTP4 should be the promoter of choice for Ad-based gene therapies of tumors deregulated for beta-catenin. We provide preliminary evidence that these may include prostate and ovarian as well as colorectal cancer.
Re: Predictive Value of a Positive Test
Authors: Christopher Fung
Journal: JAMA (1986)

<h3>To the Editor.—</h3> We wish to comment on the survey of Drs Billings and Bernstein<sup>1</sup>concerning physician appreciation of the limitations of laboratory testing in the process of clinical decision making. The authors reapplied with a slight modification the question used by Casscells et al.<sup>2</sup> In 1978, we wrote<sup>3</sup>in response to the article of Casscells et al that the question they asked in their survey could have more than one correct answer because there were several definitions of false-positive rate. Casscells et al<sup>4</sup>replied that "we left out many of the details of our interview.... We used the more generally accepted definition of false-positive rate, or ratio, and for good measure equated this result with 95% specificity and 100% sensitivity." Of course, a 5% false-positive rate can be equated with 95% specificity, but not with 100% sensitivity. In this recent survey by Drs Billings and
Cancer Drug Resistance
Authors: Tracy Hampton
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P608ANP potentiates catecholaminergic stress in early cardiac disease
Authors: R K Perera, J H Steinbrecher, S E Lehnart, V O Nikolaev
Journal: Cardiovascular Research (2014)

Purpose: Atrial natriuretic peptide (ANP) is a well-known vasodilatory factor and crucial hormone for adaptation to increased blood pressure. ANP plasma levels rise upon elevated cardiac afterload during aortic stenosis and, via guanylyl cyclase A, stimulate cardiomyocyte cGMP levels. Cardiac cGMP is considered as a protective second messenger which counteracts detrimental effects of the chronic β-adrenoceptor (β-AR)-mediated cAMP signaling. Previous studies analyzed cyclic nucleotide signaling mostly in advanced chronic heart disease. The purpose of this work was to investigate subcellular changes in cAMP/cGMP signaling and their interactions in early cardiac hypertrophy. Methods: We used a compensated cardiac hypertrophy model induced by transverse aortic constriction (TAC) in mice. Heart function was evaluated by echocardiography. Plasma ANP was quantified by ELISA. Heart rates were measured from ECG recordings in intact perfused Langendorff hearts. Cardiomyocyte (CM) contractility was analyzed by sarcomere shortening. To monitor cAMP in real time, we generated transgenic mice expressing the membrane targeted Förster resonance energy transfer (FRET) biosensor pmEpac1, localized to the sarcolemma. Individual PDE activities were measured using a classical biochemical assay. Results: 8 weeks post TAC, animals developed mild hypertrophy accompanied by a 2-fold increase in plasma ANP levels. Unexpectedly, ANP could potentiate catecholamine-induced positive chronotropic response in TAC but not sham hearts, which was accompanied by enhanced contractility in single isolated TAC CMs. FRET analysis revealed increased β1- but decreased β2-AR-cAMP signals in TAC cells without any change in β-AR densities. Interestingly, local β2-AR-associated PDE effects were dramatically altered despite unchanged whole cell PDE activities. In particular, we could uncover a switch from the PDE3- to PDE2-dependent regulation of β2-AR-cAMP signals. Since these PDEs are inversely regulated by cGMP, we tested the effect of ANP on β2-AR signaling. We found a turnaround of the cGMP/cAMP crosstalk in this microdomain, which was due to PDE2 and PDE3 redistribution and did directly translate into functional response. Conclusions: We could show that in compensated hypertrophy, elevated levels of ANP potentiate catecholamine-stimulated inotropic and chronotropic effects. This is achieved by a switch in PDE2- and PDE3-dependent regulation of β2-and β1-AR-cAMP signaling. We propose that in early cardiac disease, ANP might transiently compensate an increased demand on cardiac output.
Effect of liver transplantation on autonomic dysfunction in familial amyloidotic polyneuropathy type I
Authors: Yukio Ando, Yoshiya Tanaka, Eiko Ando, Taro Yamashita, Yasuto Nishida, Kazuhiro Tashima, Moritaka Suga, Makoto Uchino, Masayuki Ando
Journal: The Lancet (1995)
PWE-129 Pegylated Interferon Alfa, Nitazoxanide, Telaprevir, Ribavirin, in Genotype 1 Undergoing Prior Experienced Chc-A Randomized Placebo Control Clinical Pilot Trial (Intrigue-C): Abstract PWE-129 Table
Authors: P Basu, N J Shah, S Farhat, R Siriki, K Mittimanj, M Rahaman, S Atluri
Journal: Gut (2013)

<h3>Introduction</h3> Chronic Hepatitis C is a global challenge with End stage liver disease and rising Hepatocellular Carcinoma. Peg Interferon Alfa and Ribavirin was the backbone of therapy. Recently introduced Directly Acting Antivirals (DAAs)-protease inhibitors have escalated Sustained Viral Response (SVR) in Response guided therapy in non responders, partial responders and relapsers. This study utilised NTZ &amp; Telaprevir; with SOC for 24 weeks in treatment experienced patients. <h3>Methods</h3> Fifty (n = 50) patients were divided into GroupA (n = 12) NTZ 500 mg three times for 12 weeks, Group B (n = 12) NTZ, BID for 12 weeks Group C (n = 26) control. All received Peg Interferon Alfa 2a 180 mcg SQ QOW with fixed dose of Ribavirin 1200 mg daily for 24 weeks and Telaprevir 750 mg three times daily for 12 weeks. Viral load was obtained at day 0, 7th day, 14thday, 4 weeks, 12th, 24 weeks and 48th weeks SVR. Viral kinetics was analysed. In Group A, B and C: 5/12(42%), 5/12(42%), 10/26(38%) Non Responder, 6/12(50%), 6/12 (50%),4/26(15%) partial responder, and 2/12(16%), 1/12 relapsers (8%), 4/26(15%) relapsers, 2/26(8%) unknown. Use of Growth factors-12% for severe anaemia, 8% for thrombocytopenia and 7% for neutropenia. Skin rash was 29%. Rectalgia was 11%. 3/50(6%) drop out, 2/50(4%) fell in futility law. Exclusion; Decompensated liver disease. HCC, poor controlled DM, severe CAD, Hemolytic anaemia, Major depression, Renal failure, Prior severe skin rash, active drug and alcohol abuse. <h3>Results</h3> <h3>Conclusion</h3> This quadruple 24 weeks regimen has excelled the RVR, EVR, ETVT over SOC with DAAs over 11%, with SVR 67%. Needs a larger trial for validation <h3>Disclosure of Interest</h3> None Declared.
CUTANEOUS REACTIONS TO POLLEN EXTRACTS IN PATIENTS WITH HAY FEVER. SPECIAL REFERENCES TO GRASS POLLEN RECOMMENDED FOR TREATMENT IN FIXED COMBINATION
Authors: THORVALD LÖFKVIST, GUNNAR SVENSSON
Journal: Allergy (1975)

Skin reactivity to 8 common grass pollens was investigated in patients with hay fever using commercial, unfractionated extracts in serial dilution technique. The highest degree of sensitivity was observed for cocksfoot, meadow fescue, meadow foxtail, rye grass, timothy and Yorkshire fog. Five of those are included in the Allpyral 5-Grass Mix. The cutaneous responses to rye grass pollen overlap with those to timothy in a high degree.
The Deacon's Masterpiece
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1975)

THE brightest and most optimistic of my presentiments about the future of human health always seems to arouse a curious mixture of resentment and dismay among some very intelligent listeners. It is as though I'd said something bad about the future. Actually, all I claim, partly on faith and partly from spotty but unmistakable bits of evidence out of the past century of biomedical science, is that mankind will someday be able to think his way around the finite list of major diseases that now close off life prematurely or cause prolonged incapacitation and pain. In short, we will someday . . .
Confusion over use of placebos in clinical trials
Authors: J. Collier
Journal: BMJ (1995)

Better guidelines needed

“Medicine the science” is gradually replacing “medicine the art,” and demands for treatments to be evidence based have given the process a recent fillip.1 The key to this transition has been the controlled clinical trial, which, for drugs at least, is now an essential component for assessing interventions. But the clinical trial is more than a scientific instrument, for in addition to meeting the needs of the scientist it must also satisfy licensing authorities, marketing departments, prescribers, consumers, ethicists, lawyers, and often all of these in many countries. With such diverse interests, disagreements over the design of trials are inevitable, and one area in which conflict arises is in the use of the placebo.

On page 844 of this week's journal Aspinall and Goodman, who have analysed trials of ondansetron for postoperative nausea and vomiting, argue that placebos have been used so excessively that patients have been deprived of effective treatment.2 Similar concerns were raised last year about trials of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, antidepressants, and ondansetron (when used for the treatment of nausea and vomiting induced by chemotherapy).3 These allegations need addressing. Firstly, however, understanding of what determines the use of placebos is important.

Controlled clinical trials are designed to show whether a product has a pharmacological effect. Some trials seek evidence by using historical comparisons, some by comparing the product with no treatment, and others by showing a doseresponse relation for the new drug. But proof is scientifically strongest if data …
TREATMENT OF TWO HUNDRED CASES OF CHRONIC ARTHRITIS WITH MASSIVE DOSES OF VITAMIN D PREPARED BY THE WHITTIER METHOD
Authors: R. GARFIELD SNYDER
Journal: Annals of Internal Medicine (1943)

Article1 July 1943TREATMENT OF TWO HUNDRED CASES OF CHRONIC ARTHRITIS WITH MASSIVE DOSES OF VITAMIN D PREPARED BY THE WHITTIER METHODR. GARFIELD SNYDER, M.D., WILLARD HAYWOOD SQUIRES, M.D., JOHN WILFRID FORSTER, M.D., CORNELIUS HORACE TRAEGER, M.D.R. GARFIELD SNYDER, M.D.Search for more papers by this author, WILLARD HAYWOOD SQUIRES, M.D.Search for more papers by this author, JOHN WILFRID FORSTER, M.D.Search for more papers by this author, CORNELIUS HORACE TRAEGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-19-1-125_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis study was to determine (1) the toxicity and (2) the therapeutic value of treatment with massive doses of vitamin D. The dosage used varied from 100,000 to 500,000 units daily. The average dose was 200,000 to 300,000 units. Within the limits of this dosage, in over five years, no deaths occurred and no evidence of serious toxicity was observed. No definite increase in the calcification of the blood vessels, as proved by roentgenograms, occurred, nor were there any evidences of stone formations in the kidney or gall-bladder or recalcification of bones. A few cases developed mild toxic symptoms such... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAetiology and pathogenesis of rheumatoid arthritisVitamine und VitaminkrankheitenTREATMENT OF LUPUS VULGARIS WITH CALCIFEROLRheumatoid Arthritis: ReviewAdvances in the Study and Treatment of Rheumatoid Arthritis as Reported in 1942 and Part of 1943 1 July 1943Volume 19, Issue 1Page: 125-126KeywordsArthritisBlood vesselsBoneKidney stonesToxicityVitamin D ePublished: 1 December 2008 Issue Published: 1 July 1943 PDF downloadLoading ...
p53 immunoreactivity is uncommon in primary cutaneous lymphoma
Authors: J.M MCGREGOR, E.A. DUBLIN, D.A. LEVISON, D.M. MACDONALD, N.P. SMITH, S. WHITTAKER
Journal: British Journal of Dermatology (1995)

p53 gene mutation appears to play an important role in the development of systemic lymphoma, and may be associated with tumour progression. Its role in cutaneous lymphoma is currently unknown. We examined p53 expression in 55 biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis. Strong, homogeneous p53 expression, thought to correlate most closely with p53 gene mutation, was seen in only three cases; in a plaque and tumour from a patient with tumour-stage MF, in plaque-stage MF in a patient without tumours, and in one case of CD30+ large-cell anaplastic lymphoma. These data suggest that p53 gene mutation is not a critical step in the development of the majority of primary cutaneous lymphomas.
Watchful waiting is useful for children with recurrent throat infections
Authors: Paul Little
Journal: BMJ (2004)

Van Staaij et al's study is a welcome addition to a controversial subject.1 It shows that for children with moderately frequent throat infections (on average three in the previous year) a “wait and see” approach results in acceptable control of symptoms and avoids postoperative pain and complications (1% requiring operative surgery for haemorrhage, and 2.6% having severe nausea or dehydration). The major limitation of the study is the large number of children from the watchful waiting group who had tonsillectomy (34%). Since a per protocol analysis …
995-20 Effect of Hypoxia on Coronary Blood Flow and Myocardial Oxygen Extraction in Patients with Coronary Artery Disease
Authors: Achille Gaspardone, Patrizio Polisca, Filippo Crea, Fabrizio Tomai, Francesco Versaci, Maria lamele, Ruggero De Paulis, Antonio Pellegrino, Luigi Chiariello, Pier A. Gioffré.
Journal: Journal of the American College of Cardiology (1995)
Interleukin-10 inhibits hepatic injury and tumor necrosis factor-α and interferon-γ mRNA expression induced by staphylococcal enterotoxin B or lipopolysaccharide in galactosamine-sensitized mice
Authors: Masahito Nagaki, Manabu Tanaka, Akihiko Sugiyama, Hiroo Ohnishi, Hisataka Moriwaki
Journal: Journal of Hepatology (1999)
Use of Amiodarone
Authors: John R. Kapoor
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Latent Malaria presenting as Anaemia
Authors: G. Baum
Journal: BMJ (1944)

MEDRITIIURNAL 289 wvith about 20% of bloods (St-negative), all of which must therefore be homozygous RhRh and represent about half the Rh-positive homozygotes-about 38% of the population.Race and Taylor pointed out that the extent of any preponderance of homozygotes among the fathers of 'erythroblastotic children should be indicated by the proportion found to be St-negative.In 46 families in which the disease occurred and in which all the mothers were Rh-negative and had anti-Rh agglutinins in their sera, 18 of the fathers have been St-negative and 28 St- positive.If about half of the homozygotes are St-negative, then it appears that of 46 fathers about 36 were homozygous; these frequencies, compared with those expected in the general population, are:Observed St-Observed St + Estimated Estimated Homozygotes Heterozygotes 46 fathers ..
OXIDATIVE STRESS IS ASSOCIATED WITH REDUCED GLOMERULAR FILTRATION RATE IN A POPULATION WITH PRESERVED RENAL FUNCTION: THE META-HEALTH STUDY
Authors: Alanna Morris, Riyaz S. Patel, Liping Zhao, Yusuf Ahmed, Neli Stoyanova, Aurelian Bidulescu, Dorothy Coverson, Janice Lea, Viola Vaccarino, Gary Gibbons, Dean P. Jones, Rebecca Din-Dzietham, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2010)
Michigan neurosurgeon is charged with healthcare fraud for sham surgeries
Authors: O. Dyer
Journal: BMJ (2014)

A Michigan neurosurgeon could face 10 or more years in prison after the US federal government accused him of billing Medicare and commercial insurers for $33m (£21m; €27m) while performing sham lumbar spinal fusion surgeries.

Aria Sabit, 40, was arrested on 24 November and charged with five counts of healthcare fraud.1 Each of the five counts carries a maximum sentence of 10 years, which could be imposed consecutively.

In September, he was the first doctor to face criminal charges as the government tightened its scrutiny of physician owned distributorships, in which surgeons buy stakes in companies acting as middlemen for device makers and then receive a cut when they order the devices from their own distributorships to perform surgery.

Sabit was the subject of a front page story in the Wall Street Journal last year, which detailed how he profited from implants that he used in dozens of spinal fusion surgeries in California, one of which ended …