tbuckley/cabot-search huggingface dataset:
P2-12-27: Simply Adding Together the Diameters of Tumor Foci in Patients with Multicentric or Multifocal Disease Does Not Add Any Additional Prognostic Information: An Analysis from NCIC CTG MA.12 Randomized Placebo-Controlled Trial of Tamoxifen after Adjuvant Chemotherapy in Pre-Menopausal Women with Early Breast Cancer.
Authors: JF Hilton, B Dong, N Bouganim, J-AW Chapman, A Arnaout, F O'Malley, T Nielsen, K Gelmon, R Yerushalmi, M Levine, V Bramwell, T Whelan, KI Pritchard, L Shepherd, M Clemons
Journal: Cancer Research (2011)

Abstract Background: A common clinical conundrum in breast cancer management is whether pathologic T stage in women with multicentric or multifocal disease should be taken as the diameter of the largest focus or as the sum of all foci in the breast. Most staging systems, such as the American Joint Committee on Cancer (AJCC), simply use the largest tumor focus for staging. We examine here the impact of alternate methods of estimating tumour size including measures of total tumor size, volume and surface area. Materials &amp; Methods: NCIC CTG MA.12 is a randomized placebo-controlled trial of tamoxifen after adjuvant chemotherapy for pre-menopausal women with early breast cancer. Median follow up is 9.7 years. Pathologically reported patient tumor dimensions for up to 3 foci were utilized to examine the effects of tumor size on Breast-Cancer-Free-Interval (BCFI), defined as the time from randomization until recurrence (defined as first local, regional, distant, or contralateral invasive tumor or DCIS). Tumor size was estimated as 1) pathologic T stage as per AJCC criteria; 2) largest dimension of largest tumor focus (cm); 3) sum of largest dimension(s) of tumor foci (cm); 4) sum of surface area(s) of tumor foci (cm2), and 5) sum of volume of tumor foci (cm3). Step-wise forward unstratified Cox regression was used to assess the different effects of tumor size. Results: This study accrued 672 patients, 43% with T1 tumors, 51% with T2 tumors, and 6% with T3/T4 tumors; 25% were node negative and 56% had 1–3 positive lymph nodes. 75% were locally determined to have hormone receptor positive tumors. A higher number of involved lymph nodes was associated with significantly shorter BCFI (p&amp;lt;0.0001). None of pathologic T stage (p=0.14), largest dimension of largest tumor size (p=0.14), sum of largest dimensions of tumor foci (p=0.24), sum of surface area (p=0.38), and sum of volume of foci (p=0.51) were significantly associated with BCFI. Likewise, lymphovascular invasion (p=0.08), grade (p=0.14), nor administration of anthracycline therapy (p=0.08) were associated with BCFI. Discussion: In the MA.12 population of pre-menopausal women randomized to either tamoxifen or placebo, the sole factor significantly associated with BCFI was nodal status. No measure of tumor size in unifocal or multicentric/multifocal tumors impacted BCFI. The findings of this mature data set suggest that simply adding together the diameters of tumors in patients with multicentric or multifocal disease did not add any additional prognostic information. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-27.
Intrafamilial Spread of Methicillin-Resistant &lt;emph type="ital"&gt;Staphylococcus aureus&lt;/emph&gt; Infections—Reply
Authors: Robert C. Moellering
Journal: JAMA (2008)

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
Armed Oncolytic Virus Enhances Immune Functions of Chimeric Antigen Receptor–Modified T Cells in Solid Tumors
Authors: Nobuhiro Nishio, Iulia Diaconu, Hao Liu, Vincenzo Cerullo, Ignazio Caruana, Valentina Hoyos, Lisa Bouchier-Hayes, Barbara Savoldo, Gianpietro Dotti
Journal: Cancer Research (2014)

Abstract The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells remains marginal in solid tumors compared with leukemias. Failures have been attributed to insufficient T-cell migration and to the highly immunosuppressive milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells with an oncolytic virus armed with the chemokine RANTES and the cytokine IL15, reasoning that the modified oncolytic virus will both have a direct lytic effect on infected malignant cells and facilitate migration and survival of CAR-T cells. Using neuroblastoma as a tumor model, we found that the adenovirus Ad5Δ24 exerted a potent, dose-dependent, cytotoxic effect on tumor cells, whereas CAR-T cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, whereas the intratumoral release of both RANTES and IL15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor-bearing mice. These preclinical data support the use of this innovative biologic platform of immunotherapy for solid tumors. Cancer Res; 74(18); 5195–205. ©2014 AACR.
THE PRACTITIONER'S PART IN THE MOVEMENT AGAINST TUBERCULOSIS.
Authors: J. C. WILSON
Journal: JAMA (1906)

This remarkable exhibition and the popular interest it has aroused, which grows wonderfully as it is removed from one city to another, marks an epoch of transcendent importance in preventive medicine. The great pests—the oriental plague, typhus, leprosy, smallpox, typhoid fever, tuberculosis—have been the scourges of mankind through successive historical epochs because of ignorance. Enlightened modes of living and knowledge of the ways by which they spread and by which they can be prevented have restricted the prevalence of these diseases in civilized communities and greatly robbed them of their terrors. Two of them only remain to-day as world pests—typhoid fever, which could not exist in a community such as Philadelphia but for the cupidity of the spoilsman, and tuberculosis, the very existence of which as a modern plague is threatened by the spreading influence of this exhibition and the great societies under whose auspices it is held. <h3>THE MOVEMENT</h3>
HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects
Authors: Sabine Klein, Marike Marjolijn Van Beuge, Michaela Granzow, Leonie Beljaars, Robert Schierwagen, Sibel Kilic, Iren Heidari, Sebastian Huss, Tilman Sauerbruch, Klaas Poelstra, Jonel Trebicka
Journal: Journal of Hepatology (2012)
Thromboxane generation by human peripheral blood polymorphonuclear leukocytes.
Authors: I M Goldstein, C L Malmsten, H Kindahl, H B Kaplan, O Rådmark, B Samuelsson, G Weissmann
Journal: The Journal of Experimental Medicine (1978)

Human peripheral blood polymorphonuclear leukocytes were stimulated to generate thromboxane B2 in a time- and concentration-dependent fashion upon exposure to serum-treated zymosan particles. Conversion by stimulated PMN of [14C] arachidonic acid to [14C]thromboxane B2 was confirmed by thin-layer radiochromatography, radio-gas chromatography, and mass spectrometry. Generation of thromboxane B2 was independent of platelet contamination and could be inhibited by the cyclooxygenase inhibitor, indomethacin. Cells rendered incapable of ingesting particles by treatment with cytochalasin B generated comparable amounts of thromboxane B2. These results suggest that human peripheral blood polymorphonuclear leukocytes synthesize thromboxanes in response to surface stimulation independently of phagocytosis.
Abstract 4542: Regulation of the cell cycle by metformin is p21-dependent in lung cancer
Authors: Amanda Templeton, Rajagopal Ramesh
Journal: Cancer Research (2014)

Abstract The oral antidiabetic agent metformin has antineoplastic activity that is likely mediated by mechanisms independent of its hypoglycemic effects. Previously reported in human non-small cell lung carcinoma (NSCLC) cell lines, 24 h treatment with metformin induced growth inhibition and G0/G1 phase arrest through induction of the energy sensing kinase AMP-activated kinase (AMPK) and the DNA damage responsive protein ataxia telangectasia mutated (ATM). AMPK and ATM are both known to regulate G0/G1 and G2 phases through modulation of the p53-p21 axis. Therefore, the objective of our study was to elucidate the molecular mechanism of metformin induced cell cycle arrest in NSCLC. Congruent with previous findings, we demonstrate that 5mM metformin treatment for up to 72 h inhibits growth in H1299 and A549 NSCLC cell lines, but not in the non-cancerous fibroblast cell line MRC-9. In H1299 and A549 cells, growth inhibition was associated with an induction of phosphorylation of AMPK and ATM as well as a reduction in phosphorylation of AKT and mTOR. Extending these findings using H1299 cells, metformin consistently induced only a transient G0/G1 phase arrest at 24 h by downregulating cyclin D1 and p27 and upregulating p21 and at 72 h a G2/M-arrest by accumulating cyclin B1 and upregulating p21 and p27. These arrests were associated with ATM and Chk-2 activation and resultant inhibitory phosphorylation of cyclin dependent phosphatase CDC25c. Importantly, p21 knock down in H1299 cells demonstrated the coordinate loss of p27 stabilization, attenuation of the G0/G1 phase arrest at 24 h, and decrease in inhibitory phosphorylation of pan-cyclin dependent kinases. Therefore, we demonstrate for the first time in NSCLC that metformin activates G1 and G2 -checkpoint responses, but the fidelity of the G1-arrest is compromised by the downregulation of p27. However, p21-dependent upregulation of p27 facilitates a G2/M arrest at 72 h. The ability of metformin to control aberrant oncogenic cell-cycle regulation by inducing negative cell-cycle regulators p21 and p27 may provide a novel therapeutic strategy in lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Amanda Templeton, Rajagopal Ramesh. Regulation of the cell cycle by metformin is p21-dependent in lung cancer. [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 4542. doi:10.1158/1538-7445.AM2014-4542
Leptin Is an Endogenous Protective Protein against the Toxicity Exerted by Tumor Necrosis Factor
Authors: Nozomi Takahashi, Wim Waelput, Yves Guisez
Journal: The Journal of Experimental Medicine (1999)

Tumor necrosis factor (TNF) is a central mediator of a number of important pathologies such as the systemic inflammatory response syndrome. Administration of high TNF doses induces acute anorexia, metabolic derangement, inflammation, and eventually shock and death. The in vivo effects of TNF are largely mediated by a complex network of TNF-induced cytokines and hormones acting together or antagonistically. Since TNF also induces leptin, a hormone secreted by adipocytes that modulates food intake and metabolism, we questioned the role of leptin in TNF-induced pathology. To address this question, we tested mouse strains that were defective either in leptin gene (ob/ob) or in functional leptin receptor gene (db/db), and made use of a receptor antagonist of leptin. Ob/ob and db/db mice, as well as normal mice treated with antagonist, exhibited increased sensitivity to the lethal effect of TNF. Exogenous leptin afforded protection to TNF in ob/ob mice, but failed to enhance the protective effect of endogenous leptin in normal mice. We conclude that leptin is involved in the protective mechanisms that allow an organism to cope with the potentially autoaggressive effects of its immune system.
Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype
Authors: Elisabeth Tybl, Fu-Dong Shi, Sonja M. Kessler, Sascha Tierling, Jörn Walter, Rainer M. Bohle, Stefan Wieland, Jianying Zhang, Eng M. Tan, Alexandra K. Kiemer
Journal: Journal of Hepatology (2010)
481 CPA MEASUREMENT AT ONE YEAR BIOPSY IS HIGHLY PREDICTIVE OF FUTURE CLINICAL DECOMPENSATION IN HCV POST-TRANSPLANT PATIENTS RANDOMIZED IN TACROLIMUS MONOTHERAPY VERSUS TRIPLE THERAPY (TACROLIMUS-BASED)
Authors: P. Manousou, D. Samonakis, E. Cholongitas, G. Isgro, V. Calvaruso, E. Tsochatzis, D.W. Patch, J. O'Beirne, D. Thornburn, E.V. Tsianos, A.P. Dhillon, A.K. Burroughs
Journal: Journal of Hepatology (2010)
Hypertensive Effect of Erythropoietin
Authors: Julio Pascual, José L. Teruel, Joaquín Ortuño
Journal: Annals of Internal Medicine (1991)

Letters15 June 1991Hypertensive Effect of ErythropoietinJulio Pascual, MD, José L. Teruel, MD, Joaquín Ortuño, MDJulio Pascual, MDSearch for more papers by this author, José L. Teruel, MDSearch for more papers by this author, Joaquín Ortuño, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-12-1063_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:In reviewing the use of erythropoietin in patientsreceiving dialysis, Dr. Nissenson (1) asserts that the drug itself has no known direct pressor activity. Preliminary clinical and experimental data indicate that this probably is not the case (2-4). In a patient receiving hemodialysis with hypertensive encephalopathy after 8 weeks of therapy with erythropoietin, Edmunds and Walls (2) observed that the rate by which hemoglobin concentration rose was modest and that the final value was similar to that achieved with transfusions on previous occasions. Baskin and Lasker (3) recently reported the cases of five patients who had important increases...References1. Nissenson A. Recombinant human erythropoietin and renal anemia: molecular biology, clinical efficacy, and nervous system effects. Ann Intern Med. 1991;114:402-16. LinkGoogle Scholar2. EdmundsWalls MJ. Blood pressure and erythropoietin [Letter]. Lancet. 1988;1:352. Google Scholar3. BaskinLasker SL. Erythropoietin-associated hypertension [Letter]. N Engl J Med. 1990, 323:999. CrossrefMedlineGoogle Scholar4. HeidenreichRahnZidek SKW. Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int. 1991;39:259-65. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hospital Ramón y Cajal 28034 Madrid Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByErythropoietin and Its Cardiovascular Effects 15 June 1991Volume 114, Issue 12Page: 1063-1063KeywordsAttentionBrain diseasesDrugsErythropoietinHemoglobinMedical dialysis Issue Published: 15 June 1991 PDF DownloadLoading ...
Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects.
Authors: R O Bonow, V Dilsizian, D R Rosing, B J Maron, S L Bacharach, M V Green
Journal: Circulation (1985)

Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil.
The Delusive Dichotomy
Authors: Charles D. Aring
Journal: JAMA (1976)

IN AN article entitled "Thoughts on Teaching Medicine," Sir Robert Platt<sup>1</sup>said: ... After being taught... not to trust any evidence except that based on the measurements of physical science, the student has to find out for himself that all important decisions are in reality made, almost at an unconscious level, by that most perfect and complex of computers the human brain.... And the data are mostly not of the hard crude type with which that simple fellow the scientist has to deal, but are of a much more subtle, human, and interesting character, each tinted in its own colors of personality and emotion. All this the student has to discover for himself while his teachers strangely pretend to believe that the secrets of medicine are revealed only to those whose biochemical background is beyond reproach. Those subscribing to Platt's statement are likely to be uneasy with the austerity of
Diagnosis by Deduction From a Few Observations
Authors: Hugh H. Hussey
Journal: JAMA (1976)

Something more or less of Sherlock Holmes characterizes all physicians. In fact, there was so much of him in Sir Arthur Conan Doyle that a career in medicine was sacrificed, and the narration of Holmes's exploits became the writer's abiding interest and means of livelihood. As told by Doyle through the person of Dr Watson, Holmes's success as a consulting detective was based on his remarkable ability to observe and to deduce the right conclusions from his observations—powers that continually amazed Watson. Indeed, when the two fictional characters first meet in<i>A Study in Scarlet</i>, Holmes puzzles Watson by describing him as a physician lately engaged in military service in Afghanistan. The dialogue between the two friends is self-explanatory. HOLMES: You appeared to be surprised when I told you, on our first meeting, that you had come from Afghanistan. WATSON: You were told, no doubt. HOLMES: Nothing of the sort.
Abstract 5353: Identification of a subset of AIDS related lymphoma (ARL) containing HIV infected macrophages that is immunophenotypically distinct from EBV+ ARL
Authors: Leanne C. Huysentruyt, Paige M. Bracci, Michael S. McGrath
Journal: Cancer Research (2010)

Abstract The risk of developing non-Hodgkin lymphoma is 60X greater in the HIV-infected population when compared to non-infected individuals despite the initiation of highly active antiretroviral therapy (HAART). The primary difference between lymphoma in non-infected individuals and those with AIDS related lymphoma (ARL) is that ARL is high-grade and metastatic. Since the introduction of HAART the incidence of ARL has decreased but not the same extent as other AIDS-related malignancies and there has been little change amongst the CD4 strata. Therefore, with the increase in life expectancy afforded by HAART, the overall number of ARL cases is expected to rise in the future. Preliminary reports have suggested that some ARLs contain HIV-infected macrophages that may contribute to ARL pathogenesis. A recent study evaluating HIV sequence evolution in the contest of metastatic ARL found lymphoma specific HIV compartmentalized within sites of lymphoma that was distinct from HIV present in non-lymphoma sites (Salemi et al, PLOSone Dec 3, 2009). These data suggested the existence of a lymphoma specific form of HIV evolving within individuals who develop ARL. The goal of this research was to determine the incidence of HIV infected lymphomas in the pre and post-HAART eras and if HIV-positive lymphomas have a specific immunophenotype. A tissue microarray containing ∼150 of ARLs (from 1982-2007) was obtained through the AIDS and Cancer Specimen Resource (ACSR) and was used for HIV p24 and macrophage CD68 immunohistochemistry. Double staining techniques confirmed that p24 expression was localized to tumor associated macrophages (TAM). There was a highly significant (p&amp;lt;0.001) increase in the frequency of p24+ ARL cases post-HAART (after 1996; 49%) as compared to pre-HAART (before 1996; 26%). Using antigen expression data CD20, CD3, CD10, BCL6, BCL2, MUM1, Ki67, blimp, p53 and EBV, provided by the ACSR, we were able to determine that p24+ ARLs were generally of B cell origin but did not have a specific immunophenotype. In contrast, EBV+ ARLs were more likely to express MUM1 or blimp and less likely to express CD29, CD10 or BCL6. EBV status was not associated with a pre/post HAART diagnosis (44 vs. 40%). However, a subset of EBV-/p24+ tumors was identified. In the pre-HAART era, 13% of the tumors were EBV-/p24+ compared to 30% in the post-HAART era suggesting, that the incidence of this tumor type is increasing (p&amp;lt;0.05). These data describe for the first time the existence of potentially tumor specific HIV in up to 1/3 of all post HAART ARLs, a class of tumor that is immunophenotypically distinct from EBV+ ARLs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5353.