tbuckley/cabot-search huggingface dataset:
Abstract 2900: IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma
Authors: Namir J. Hassan, Giovanna Bossi, Debbie Baker, Katherine Adams, Jane Harper, Joseph Dukes, Nathaniel Liddy, Samantha Paston, Yvonne McGrath, Tara Mahon, Peter Molloy, Malkit Sami, Emma Baston, Brian Cameron, Andrew Johnson, Annelise Vuidepot, Gerry Linette, Michael Kalos, Carl June, Bent Jakobsen
Journal: Cancer Research (2014)

Abstract Despite significant advances in the treatment of metastatic melanoma, long-term remission for the majority of patients remains elusive. Kinase inhibitors provide potent but short-term responses for a significant proportion of patients and immunotherapy elicits long-term responses with the prospect of cure, but only in a minority. IMCgp100 is a novel bi-specific immunotherapy comprising a soluble, affinity enhanced, T cell receptor (TCR) specific for the melanoma-associated antigen gp100, fused to an anti-CD3 specific antibody fragment (scFv). The engineered TCR portion of the drug targets and binds the gp100 peptide 280-288 antigen, which is over-expressed and presented by HLA-A2 on the surface of melanoma cells. The anti-CD3 scFv portion captures and redirects T cells to kill the melanoma cells, while normal antigen negative tissues are unaffected. Here, we present data which provides the foundation for the clinical observations. In vitro, IMCgp100 is demonstrated to potently redirect T cells from late stage cancer patients to target melanoma tumors exhibiting HLA-down regulation, even in the presence of high numbers of regulatory T cells. Target cell killing is observed within hours and is specific for gp100. In addition killing is associated with the release of various pro-inflammatory cytokines and chemokines as well as cross-presentation of gp100 and other melanoma-associated antigens by dendritic cells. Thus, IMCgp100 demonstrates the potential to elicit potent short-term responses and trigger longer-term anti melanoma activity in vivo. IMCgp100 is undergoing Phase I clinical testing in patients with advanced malignant melanoma; with the maximum tolerated dose having been established. The drug is well tolerated with evidence of tumor shrinkage. Analyses of serum samples obtained from patients on the trial demonstrate T cell mobilisation and transient drug mediated increases in various cytokines and chemokines, some of which are reported to play a key role in anti-melanoma responses. These data support the potential of IMCgp100 as an effective treatment for malignant melanoma. Citation Format: Namir J. Hassan, Giovanna Bossi, Debbie Baker, Katherine Adams, Jane Harper, Joseph Dukes, Nathaniel Liddy, Samantha Paston, Yvonne McGrath, Tara Mahon, Peter Molloy, Malkit Sami, Emma Baston, Brian Cameron, Andrew Johnson, Annelise Vuidepot, Gerry Linette, Michael Kalos, Carl June, Bent Jakobsen. IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma. [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 2900. doi:10.1158/1538-7445.AM2014-2900
Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2V617F in mice
Authors: Christoph Walz, Wesam Ahmed, Katherine Lazarides, Monica Betancur, Nihal Patel, Lothar Hennighausen, Virginia M. Zaleskas, Richard A. Van Etten
Journal: Blood (2012)
Activity of Broad-Spectrum T Cells as Treatment for AdV, EBV, CMV, BKV, and HHV6 Infections after HSCT
Authors: Anastasia Papadopoulou, Ulrike Gerdemann, Usha L. Katari, Ifigenia Tzannou, Hao Liu, Caridad Martinez, Kathryn Leung, George Carrum, Adrian P. Gee, Juan F. Vera, Robert A. Krance, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. Leen
Journal: Science Translational Medicine (2014)

Rapidly generated broad-spectrum T cells can simultaneously treat multiple viral infections after hematopoietic stem cell transplant.
Marginal to Mainstream: Alternative Medicine in America
Authors: Brent A. Bauer
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes17 August 2004Marginal to Mainstream: Alternative Medicine in AmericaBrent A. Bauer, MDBrent A. Bauer, MDFrom Complementary and Integrative Medicine Program, The Mayo Clinic, Rochester, Minnesota.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-4-200408170-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Ruggie M. 232 pages. Cambridge, United Kingdom: Cambridge Univ Pr; 2004. $65.00. ISBN 0521834295. Order phone 212-924-3900.Field of medicine: Complementary and alternative medicine (CAM) and integrative medicine.Format: Hardcover book.Audience: Physicians and researchers interested in CAM or integrative medicine, especially in relation to the historical development and growth of this field.Purpose: To describe the “transformation in the status of alternative medicine within health care” from a marginal consideration in the late 1980s to an increasingly mainstream option or adjunct in 2004. In the process, the author addresses such questions as, What is CAM? Why are so many ... Author, Article, and Disclosure InformationAffiliations: From Complementary and Integrative Medicine Program, The Mayo Clinic, Rochester, Minnesota. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 August 2004Volume 141, Issue 4Page: 328KeywordsComplementary and alternative medicineForecastingHealth careSoftware tools ePublished: 17 August 2004 Issue Published: 17 August 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cancer Stem Cells: Targets and Potential Biomarkers for Radiotherapy
Authors: Mechthild Krause, Ala Yaromina, Wolfgang Eicheler, Ulrike Koch, Michael Baumann
Journal: Clinical Cancer Research (2011)

Cancer stem cells (CSC) have the unique ability to cause tumor recurrences if they survive treatment. Radiotherapy has curative potential because it has been functionally shown to sufficiently inactivate CSCs. It is well known that CSCs mediate the radiation resistance of tumors by tumor-specific factors, such as the pretreatment number of CSCs and repopulation or reoxygenation during fractionated radiotherapy. CSCs appear to have a higher intrinsic radioresistance than non-CSCs, a factor that is especially important for the development of predictive biomarkers that, if this finding holds true, can only be successfully established if they are stem-cell specific. Recent clinical data imply that stem-cell-related surface markers may be directly used as predictors for the radiocurability of tumors with comparable risk factors, such as histology and size. Future studies need to address the question of which additional markers need to be considered if more heterogeneous patient collectives are investigated. With the goal of developing a direct targeting approach, investigators are currently evaluating several drugs that are intended to target CSCs by inhibiting stem-cell-related signal transduction pathways. We need to preclinically test such drugs as combined-modality therapies in combination with radiotherapy to evaluate their curative potential, and optimize them by increasing their specificity to CSCs over normal tissue stem cells to avoid increased radiation toxicity.
Perspectives on clinical leadership: a qualitative study exploring the views of senior healthcare leaders in the UK
Authors: Edward D Nicol, Kay Mohanna, Jenny Cowpe
Journal: Journal of the Royal Society of Medicine (2014)

Introduction Clinicians are being asked to play a major role leading the NHS. While much is written on about clinical leadership, little research in the medical literature has examined perceptions of the term or mapped the perceived attributes required for success. Objective To capture the views of senior UK healthcare leaders regarding their perception of the term `clinical leadership' and the cultural backdrop in which it is being espoused. Setting UK Healthcare sector Participants Senior UK Healthcare leaders Methods Twenty senior healthcare leaders including a former Health Minister, NHS Executives, NHS Strategic Health Authority, PCT and Acute Trust chief executives and medical directors, Medical Deans and other key actors in the UK medical leadership arena were interviewed between 2010 and 2011 using a semi-structured interview technique. Using grounded theory, themes were identified and subsequently analysed in an attempt to answer the broad questions posed. Main outcome measures Not applicable for a qualitative research project Results A number of themes emerged from this qualitative study. First, there was evidence of changing attitudes among doctors, particularly trainees, towards becoming involved in clinical leadership. However, there was unease over the ambiguity of the term ‘clinical leadership’ and the implications for the future. There was, however, broad agreement as to the perceived attributes and skills required for success in healthcare leadership. Conclusions Clinical leadership is often perceived to be doctor centric and ‘Healthcare Leadership’ may be a more inclusive term. An understanding of the historical medico-political context of the leadership debate is required by all healthcare leaders to fully understand the challenges of changing healthcare culture. Whilst the broad attributes deemed essential for success as a healthcare leaders are not new, significant effort and investment, including a physical Healthcare Academy, are required to best utilise and harmonise the breadth of leadership talent in the NHS.
Antihypertensive Treatment of Patients With Cardiovascular Disease but Without Hypertension—Reply
Authors: Angela M. Thompson
Journal: JAMA (2011)

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
Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease.
Authors: S H Murch, V A Lamkin, M O Savage, J A Walker-Smith, T T MacDonald
Journal: Gut (1991)

Serum tumour necrosis factor alpha (TNF alpha) concentrations were measured by enzyme linked immunoadsorbent assay in 31 normal children and during 65 episodes of clinical remission and 54 episodes of relapse in 92 children with chronic inflammatory bowel disease. An appreciable rise in TNF alpha was found only in children in relapse of ulcerative colitis and colonic Crohn's disease. The group of children with small bowel Crohn's disease in relapse did not show increases of TNF alpha above control concentrations, despite an equivalent rise in disease indices. Height velocity was depressed in children with relapse of large bowel Crohn's disease and ulcerative colitis compared with the equivalent condition in remission. The impairment of growth velocity was significantly greater in relapse of large bowel Crohn's disease and ulcerative colitis than in small bowel Crohn's disease alone, although for the subgroups in stage 1 puberty (prepubertal) the differences were not significant. Inadequate growth in chronic inflammatory bowel disease is currently ascribed to inadequate nutrition and TNF alpha may contribute to this through its cachexia inducing effects. It may, in addition, diminish pituitary growth hormone release. These results suggest that production of TNF alpha may be associated with growth failure in relapse of colonic inflammatory bowel disease.
Special Communication from the National Cancer Institute: Survival After Breast-Sparing Surgery Versus Mastectomy
Authors: J. Abrams, T. Chen, R. Giusti
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Special Communication from the National Cancer InstituteSurvival After Breast-Sparing Surgery Versus Mastectomy Get access Jeffrey Abrams, M.D., Jeffrey Abrams, M.D. NCI'S Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy Chen, Ph.D., Timothy Chen, Ph.D. NCI'S Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruthann Giusti, M.D. Ruthann Giusti, M.D. NCI'S Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 22, 16 November 1994, Pages 1672–1673, https://doi.org/10.1093/jnci/86.22.1672 Published: 16 November 1994
Abstract P6-05-21: High standardized uptake value of 18F-fluorodeoxy-glucose positron emission tomography is related with FOXM1 expression, which negatively influences survival in breast cancer patients
Authors: SG Ahn, HM Lee, HW Lee, SA Lee, S-H Leem, J Jeong, I-S Chu
Journal: Cancer Research (2013)

Abstract Background Standardized uptake value (SUV), which is an indicator reflecting glucose uptake in 18F-fluorodeoxy-glucose positron emission tomography (18FDG-PET), can be implicated to be a prognostic factor in various malignant tumors. Using a data set with gene expression profiling, we tried to uncover a molecular marker associated with a high SUV, along with an exploration its prognostic value in breast cancer. Methods Microarray gene expression profiling was performed in 287 breast tumor samples. Five hundred nanograms of total RNA were used for labeling and hybridization, according to the manufacturer's protocols (Illumina, San Diego, CA). In 66 samples with SUV, genes with expression patterns highly correlated with the value of SUV were selected for cluster analysis. Five hundred thirty tree gene features were selected for analysis. Patients were divided into the following two groups: SUV-high cluster and SUV-low cluster. Hierarchical clustering analysis based on 533 gene features. The prognostic value of the identified gene was validated in 287 samples and the online public set. Results Gene network analysis using Ingenuity Pathway Analysis software revealed considerable enrichment of the gene network toward FOXM1 in the SUV-high cluster, suggesting that its activation might be a key determinant associated with SUV level. Also, the expression of many marker genes for cell proliferation, such as AURKA, AURKB, BIRC5, BUB1, and TOP2A, was significantly higher in the SUV-high cluster than in the SUV-low cluster. Next, in the 287 patients with known FOXM1 expression levels, the Kaplan-Meier survival analysis revealed a negative prognostic impact of highly expressed FOXM1 for overall survival (OS), disease-free survival (DFS), and distant-metastasis-free survival (DMFS) (P = 0.002, P = 0.015, P = 0.008, respectively; Table 1). To validate a prognostic impact of FOXM1 in an external data, we performed a survival analysis using online gene-expression array data. There was significant correlation between the FOXM1 expression level and OS, DFS and DMFS. Conclusion Here we analyzed FOXM1 as a biomarker associated with a high SUV and demonstrated that FOXM1 is a negative prognostic factor in breast cancer. Prognostic significance of FOXM1 in 287 patients Overall SurvivalBreast cancer-specific survivalDisease-free survivalDistant metastasis-free survivalFOXM1 high (n = 144)log-rank testlog-rank testlog-rank testlog-rank testFOXM1 low (n = 133)P = 0.002P = 0.001P = 0.015P = 0.008 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-21.
Treatment With Clopidogrel After Myocardial Infarction
Authors: Roy C. Ziegelstein
Journal: JAMA (2012)

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
Impact of an Annual Dollar Limit or "Cap" on Prescription Drug Benefits for Medicare Patients
Authors: Chien-Wen Tseng, Robert H Brook, Emmett Keeler, Carol M Mangione
Journal: JAMA (2003)

Annual dollar limits, or "caps," on drug benefits are common in Medicare managed care (Medicare + Choice) and have been part of several proposals for a national Medicare drug benefit.To determine how cap levels affect the percentage of patients exceeding the cap and their out-of-pocket drug costs and to identify the medications that contribute most to prescription costs.Cross-sectional analysis of 2001 pharmacy claims data from a large Medicare + Choice plan in a mature market with caps of 750 dollars to 2000 dollars per year applied to the plan's share of prescription costs.Patients who filled at least 1 prescription in 2001 (n = 438 802).Percentages of patients exceeding caps, identified from prescription claims; out-of-pocket patient costs before exceeding caps, calculated from patients' co-payments; and out-of-pocket patient costs after exceeding caps, estimated from total prescription costs before exceeding the cap. Each unique drug was ranked by total expenditures, which included spending by patients who exceeded caps and by the plan for that drug.A total of 22%, 14%, and 4% of Medicare patients exceeded caps of 750 dollars, 1000 dollars, and 2000 dollars, respectively. Across caps, patients faced a potential 2- to 3-fold increase in median out-of-pocket costs after exceeding caps (179 dollars-305/mo dollars) to continue the same prescription use as before exceeding caps (79-100/mo dollars). For patients who exceeded a cap of 750 dollars, yearly out-of-pocket drug costs ranged from 564 dollars to 4201 dollars (5th-95th percentiles). Fifteen of the 20 medications with the highest total prescription expenditures for patients who exceeded the cap were for chronic conditions. Seven had lower-cost generic versions or a generic medication available in the same treatment class.At lower caps, a substantial proportion of Medicare patients exceeded their annual drug benefit. To continue the same medication use as before exceeding caps, these patients faced potentially high increases in out-of-pocket costs for medications used primarily to treat chronic conditions. Generic options were not available for many of these drugs.
Longest-stay patients.
Authors: D A Spencer
Journal: BMJ (1979)

Retroperitoneal fibrosis after treatment with atenolol SIR,-The report from Belfast City Hospital (23-30 December, p 1786) implying that atenolol may have been the cause of retroperitoneal fibrosis in a 68-year-old woman deserves comment.There are several reasons for supposing that the suspicion of a cause- and-effect relationship is not well founded.The authors state that this case was reported "because of the established relationship between the earlier beta-blocker practolol and similar types of sclerosing fibroblastic reaction."However, in more than 200 cases of
Internet sales threaten drug companies supremacy
Authors: A. Tuffs
Journal: BMJ (2002)

A row is brewing over the announcement by a German health insurance company that patients should buy their drugs over the internet to cut costs—a move that threatens to undermine the monopoly of the German pharmaceutical industry.

The Bavarian health insurance company Bayerische Betriebskrankenkassen recently set up a contract with the Dutch internet pharmacy shop DocMorris and has advised its 1.8 million members to order cheaper drugs via the internet. This would enable them to fill prescriptions at lower cost than at a pharmacy and would also allow them to buy non-prescription drugs more cheaply.

The Bavarian company's website tells members: “You can use DocMorris. Refundable drugs will be refunded by us, just like …
Randomized Prospective Trial of Continuous vs Intermittent Heparin Therapy
Authors: Richard L. Glazier
Journal: JAMA (1976)

Forty-one patients with clinical indications for heparin therapy were randomized to receive continuous intravenous heparin sodium therapy or intermittent (four-hourly bolus) heparin therapy, with control by the activated partial thromboplastin time. Seven of 21 patients receiving intermittent therapy had major bleeding episodes, whereas none of the 20 patients receiving continuous heparin therapy had major bleeding (P = .005). One patient on continuous therapy had a pulmonary embolus, while none on intermittent therapy had recurrent thromboembolism. Two heavily bleeding patients on intermittent therapy were switched to continuous treatment after bleeding was controlled. The use of continuous heparin therapy appears significantly safer with regard to hemorrhagic complications than the use of intermittent therapy.
The Case for a Parental Duty to Use Preimplantation Genetic Diagnosis for Medical Benefit
Authors: Janet Malek, Judith Daar
Journal: The American Journal of Bioethics (2012)

This article explores the possibility that there is a parental duty to use preimplantation genetic diagnosis (PGD) for the medical benefit of future children. Using one genetic disorder as a paradigmatic example, we find that such a duty can be supported in some situations on both ethical and legal grounds. Our analysis shows that an ethical case in favor of this position can be made when potential parents are aware that a possible future child is at substantial risk of inheriting a serious genetic condition. We further argue that a legal case for a duty to use PGD for medical benefit can be made in situations in which potential parents have chosen to conceive through in vitro fertilization and know that any children conceived are at substantial risk of having a serious genetic condition.