tbuckley/cabot-search huggingface dataset:
Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer
Authors: Daniele Viarisio, Karin Müller-Decker, Paola Zanna, Ulrich Kloz, Birgit Aengeneyndt, Rosita Accardi, Christa Flechtenmacher, Lutz Gissmann, Massimo Tommasino
Journal: Cancer Research (2016)

Abstract The beta genus of human papillomaviruses (ß-HPV) includes approximately 50 different viral types that are subdivided into five species (ß-1 through ß-5). Nonmelanoma cancers may involve some ß-1 and ß-2 HPV types, but the biology of most ß-HPV types and their possible connections to human disease are still little characterized. In this study, we studied the effects of ß-3 type HPV49 in a novel transgenic (Tg) mouse model, using a cytokeratin K14 promoter to drive expression of the E6 and E7 genes from this virus in the basal skin epidermis and the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene expression only marginally increased cellular proliferation in the epidermis of Tg animals, compared with wild-type littermates, and we observed no spontaneous tumor formation during their entire lifespan. However, we found that K14 HPV49 E6/E7-Tg mice were highly susceptible to upper digestive tract carcinogenesis upon initiation with 4-nitroquinoline 1-oxide (4NQO). This was a selective effect, as the same mice did not exhibit any skin lesions after chronic UV irradiation. Opposite results were observed in an analogous Tg model expressing the ß-2 HPV38 E6 and E7 oncogenes at the same anatomic sites. While these mice were highly susceptible to UV-induced skin carcinogenesis, as previously shown, they were little affected by 4NQO treatment. Overall, our findings highlight important differences in the biologic properties of certain ß-type HPV that affect their impact on carcinogenesis in an anatomic site-specific manner. Cancer Res; 76(14); 4216–25. ©2016 AACR.
Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment
Authors: E Terpos, M Migkou, D Christoulas, M Gavriatopoulou, E Eleutherakis-Papaiakovou, N Kanellias, M Iakovaki, I Panagiotidis, D C Ziogas, D Fotiou, E Kastritis, M A Dimopoulos
Journal: Blood Cancer Journal (2016)

Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.
Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal
Authors: E Klein, T W Uhde, R M Post
Journal: American Journal of Psychiatry (1986)

Alprazolam treatment is effective for panic disorder, but its major disadvantages include possible dependence and withdrawal symptoms upon discontinuation. The authors report three cases in which carbamazepine, a clinically effective anticonvulsant without abuse potential, successfully attenuated alprazolam withdrawal symptoms.
Abstract P5-07-08: The clinical utility of alternative chromosome 17 probes in equivocal HER2 results
Authors: N Sneige, Y Gong, AS Multani, NK Ibrahim
Journal: Cancer Research (2016)

Abstract Background Acurrate assessment of HER2 status in patients with breast cancer is critical in selecting patients for targeted therapy. In 2013, the American Society of Clinical Oncology-/College of American Pathologists (ASCO/CAP) released new guidelines for HER2 testing in an attempt to more acurately identify all breast cancer patients who are eligible for HER2 targeted therapy; these guidelines included new cutoff points for HER2/CEP17 ratio by in situ hybridization (ISH) or average HER2 copy number/cell and recommended the use of a reflex test with alternative ISH chromosome 17 probe for resolving cases with equivocal HER2 ISH results. We sought to determine the clinical utility of alternative chromosome 17 probes in such equivocal cases. Patients and Methods Our institution's database of HER2 dual- probe ISH results was searched for cases of invasive breast cancer with a HER2/CEP17 ratio of &amp;lt;2 and an average HER2 copy number of &amp;gt;4 and &amp;lt;6 signals/cell (i.e., cases meeting the new ASCO/CAP definition of equivocal). Of these, 30 consecutive cases with available corresponding sections were selected for additional chromosome 17 studies using probes for Smith-Magenis syndrome (SMS) and retinoic acid receptor alpha (RARA) genes. A eusomic copy number exhibited in one or both of these loci was used to calculate a revised HER2/chromosome-17 ratio by using the eusomic gene locus as the reference. Results Of 5489 cases of invasive breast cancer tested by dual-probe ISH for HER2 gene status, 316 (5.7%) cases were found to have equivocal results according to the 2013 ASCO/CAP guidelines. Further analysis of the 30 equivocal consecutive cases using the alternative chromosome 17 probes (SMS/RARA), 17 cases were upgraded from equivocal to positive HER2 status, and 13 cases remained unchanged. Conclusion The use of alternative chromosome 17 probes effectively determines true HER2 status in most equivocal HER2 ISH cases. Equivocal results are common; therefore, we advocate testing for alternative chromosome 17 genes to better categorize equivocal cases under the new ASCO/CAP guidelines. Additional analysis of the remaining equivocal cases and their relation to disease progression is underway and will be presented at the meeting. Citation Format: Sneige N, Gong Y, Multani AS, Ibrahim NK. The clinical utility of alternative chromosome 17 probes in equivocal HER2 results. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-07-08.
Blockers
Authors: Jack Coulehan
Journal: Annals of Internal Medicine (2002)

On Being a Doctor5 March 2002BlockersJack Coulehan, MDJack Coulehan, MDDr. Coulehan: Setauket, NY 11733Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-5-200203050-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The guy's an iceberg. I feel the cold breeze the moment I walk into the office, where he stands beside the examining table, his arms crossed, a thin man, pale eyes, dour face, measured stare. I'd say he's about 40 and prematurely bald.Maybe iceberg isn't right. How about an oven? I get the feeling he might explode at any second. Or minefield. That's it; he's a walking minefield. I've heard there are millions of mines left over from the war in Western Europe, tens of millions in Southeast Asia. Here on Long Island, we have minefields, too, but they're ... Author, Article, and Disclosure InformationAuthors: Jack Coulehan, MDAffiliations: Dr. Coulehan: Setauket, NY 11733Corresponding Author: Jack Coulehan, MD, 4 Townsend Court, Setauket, NY 11733 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 March 2002Volume 136, Issue 5Page: 407-409KeywordsBlood pressureCholesterolDrugsGamma aminobutyric acidNeuronsNeurotransmittersPotassiumScientistsVitaminsWalking ePublished: 5 March 2002 Issue Published: 5 March 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract IA04: How DNA methylation organizes the cancer epigenome
Authors: Peter A. Jones
Journal: Cancer Research (2016)

Abstract The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. We performed a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG Island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome depleted regions, respectively. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multi-scale organization of cancer epigenomes. Citation Format: Peter A. Jones. How DNA methylation organizes the cancer epigenome. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr IA04.
Q&A: Muin Khoury on Cancer Epidemiology
Authors: Muin J Khoury, Suzanne Rose
Journal: Cancer Discovery (2014)

Muin J. Khoury, MD, PhD, director of the Centers for Disease Control and Prevention's Office of Public Health Genomics and head of the National Cancer Institute's Epidemiology and Genomics Research Program in the Division of Cancer Control and Population Sciences, talks about challenges and opportunities in cancer epidemiology research and efforts in the epidemiology community to transform the field.
Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program
Authors: S M Sotsky, D R Glass, M T Shea, P A Pilkonis, J F Collins, I Elkin, J T Watkins, S D Imber, W R Leber, J Moyer
Journal: American Journal of Psychiatry (1991)

The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program.Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory).One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy.The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.
Abstract P2-09-06: Multi-gene panel testing for hereditary cancer risk
Authors: S Yadav, R Ladkany, J Fulbright, H Dreyfuss, A Reeves, S Campian, V Thomas, D Zakalik
Journal: Cancer Research (2016)

Abstract Background: Multi-gene panels are widely available for assessing hereditary cancer risk in high risk individuals. Due to the use of these panels, many genetic mutations other than BRCA 1 or 2 can be detected which can potentially affect management. This study presents the results of multi-gene panel testing performed at Beaumont Health System. Methods:All patients who underwent multi-gene panel testing at Beaumont Health System between November 1, 2012 and January 15, 2015 were included in this study. This cohort consisted of patients who met criteria for genetic testing due to personal or family history. All patients received comprehensive pre and post-test genetic counseling. The panels ranged from 5 to 43 genes associated with risk for breast and other cancers. Results: 653 multi-gene panel tests were performed. The majority of these consisted of either a 5 gene high risk breast panel (25%), an 18 gene moderate to high risk breast panel (21%), or a 9 gene high risk breast and gynecologic panel (17%). 184 variants of undetermined significance (VUS) were identified with a pooled VUS rate of 28%. Among the commonly used panels, there was a positive correlation between VUS rate and the number of genes included in the panel (r = 0.86, p = 0.01, Range 6% to 70%). A pathogenic mutation was identified in one or more genes in 65 (10%) panels for a total of 67 mutations. Of these, 17 mutations were in BRCA1 or BRCA2 gene. Fifty non-BRCA deleterious mutations were identified with the following frequencies: CHEK2(12), MUTYH(7 monoallelic, 1 biallelic), TP53(4), PTEN(4), ATM(4), MSH6(3), PALB2(3), MSH2(2), CDH1(2), APC(2), NF1(2), BARD1(2), MLH1(1) and PMS2(1). Of these non-BRCA mutations, 41(82%) had a significant impact on management. Conclusions: Our study demonstrates that multi-gene panel testing identifies several genes that can impact management and would likely not have been discovered by pedigree analysis alone. However, this added detection is associated with a higher VUS rate, especially using larger panels. Further research is needed to better define the role of multi-gene panel testing in high risk patients, with a focus on choosing appropriate genes, understanding the magnitude of cancer risk and delineating impact on management. Citation Format: Yadav S, Ladkany R, Fulbright J, Dreyfuss H, Reeves A, Campian S, Thomas V, Zakalik D. Multi-gene panel testing for hereditary cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-06.
A comparison of two unilateral ECT electrode placements: efficacy and electrical energy considerations
Authors: M K Erman, C A Welch, M R Mandel
Journal: American Journal of Psychiatry (1979)

The authors compared the treatment outcomes and ECT energy requirements of 10 patients treated with the Muller unilateral placement method (secondary electrode in the frontal position) with those of 10 matched patients treated with the unilateral placement described by d'Elia (secondary electrode lateral to the vertex). Both groups showed a similar dramatic clinical improvement after ECT; however, the mean watt seconds required for the Muller method was nearly four times that for the d'Elia procedure. The treating physicians reported that the patients treated by the d'Elia method had fewer anterograde and retrograde memory disturbances and that they were alert and oriented sooner after ECT.
Comparison of Cox Model Methods in a Low-Dimensional Setting with Few Events
Authors: Francisco M. Ojeda, Christian Müller, Daniela Börnigen, David-Alexandre Trégouët, Arne Schillert, Matthias Heinig, Tanja Zeller, Renate B. Schnabel
Journal: Genomics Proteomics & Bioinformatics (2016)

Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i) full model using all available predictors and estimated by standard techniques, (ii) backward elimination (BE), (iii) ridge regression, (iv) least absolute shrinkage and selection operator (lasso), and (v) elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD), we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches. Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.
Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis.
Authors: Pearlman As
Journal: Circulation (1991)

The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment.
Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy
Authors: Wantong Song, Zhaohui Tang, Dawei Zhang, Xue Wen, Shixian Lv, Zhilin Liu, Mingxiao Deng, Xuesi Chen
Journal: Theranostics (2016)

Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors.However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues.Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy.Specifically, combretastatin A-4 (CA4) serves as a "cannon" by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a "pawn" by killing tumor cells in close proximity to blood vessels.This "cannon and pawn" combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor.In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection.In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm 3 ), this strategy also proved effective for inhibiting tumor growth.These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy.
THE NOMENCLATURE OF MALARIA: A Suggestion
Authors: D. Bruce
Journal: BMJ (1903)

Since this lecture was given, [ have done four more cases, making twenty-six in a'l.One of these four cases was the hardest I have yet hau; and I have failed, even witlh two operations, to do much good.The nose had been absolutely flat for half a century, and the skin was almost hopelessly rigid: and a preliminary use of the tenotomy knife caused some bleeding.Happily, I have done no harm, and some good; and shall be able to do more, a few weeks hence; but it is a disappointing case.Such intense tightness and unyielding rigidity of the skin are altogether exceptional.To sum up-I have had twenty-six cases without death or disaster; and the general results are very good.In nine cases out of ten, the surgeon can be sure of making a very great improvement: but he may not be able to do it all at once.He cannot make perfect noses; but he can make the patients good looking enough to be happy instead of miserable, and able to get work, to get married, and to go about without being ridiculed, pitied, or suspected of syphilis.Only.let nobody think that the method is so easy as it sounds.It is full of little difficulties; it wants experience; and it involves very grave responsibility.