tbuckley/cabot-search huggingface dataset:
Phase II trial of Ontak to deplete regulatory T cells in treatment-refractory stage III/IV ovarian cancer
Authors: Brian G. Barnett, Jens Ruter, Pui J. Cheng, Inka Kryczek, Michael Brumlik, Jonathan Head, Robert Elliott, Weiping Zou, Tyler J. Curiel
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4885 

This Phase II trial tests whether Ontak (denileukin diftitox) is useful to treat epithelial ovarian cancer, stages III or IV that have failed first-line therapy with optimal surgical debulking and platinum-based chemotherapy. Ontak is a fusion toxin consisting of interleukin-2 genetically fused to diphtheria toxin. It is approved to treat cutaneous T cell leukemia/lymphoma. Our recent Phase I trial demonstrated that Ontak depletes human regulatory T cells (Tregs), associated with improved measures of T cell immunity and associated with clinical improvements in ovarian cancer. Based on Phase I results, we initiated a Phase II clinical efficacy trial in treatment-refractory epithelial ovarian cancer using Ontak 12 micrograms/kilogram once monthly. In the Phase II design, patients received no chemotherapy for at least two weeks and no immune or radiation therapy for at least four weeks prior to enrollment. Infusion pretreatment is antihistamines, acetaminophen and anti-emetics, but no steroids. Five patients (FIGO1,2,4-6) have been treated to date. FIGO1 experienced CA-125 stabilization and approximately 20% reduction in her pelvic mass after two cycles, but was then withdrawn for hypoalbuminemia. FIGO2 experienced CA-125 stabilization after two cycles. FIGO4 experienced a 20% drop in CA-125 after two cycles, but then progressed. FIGO5 progressed after one cycle. Immune analyzes are currently incomplete post-Katrina. Existing data confirm that Ontak treatment in the Phase II trial is associated with reductions in phenotypic CD4+CD25hi blood Tregs and increased CD3+IFN-g+ T cells consistent with our Phase I results. Studies of Treg function, T cell cytokine production and CD4+CD25+ T cell FOXP3 content will be undertaken shortly when full laboratory operations resume using saved clinical material. The trial continues to accrue patients. These data suggest that Ontak depletes Tregs in ovarian cancer. The link between Treg depletion and any observed immune changes or clinical effects is under active investigation, and remains to be determined.
Brief Communication: A Simple Cell-Suspension Method for Transplantation of V2 Carcinoma2
Authors: Daniel M. Berkowitz, Leslie Alexander, Norman K. Hollenberg
Journal: JNCI Journal of the National Cancer Institute (1975)

A simple and rapid method for the preparation of an essentially monodispersed cell suspension from the rabbit V2 carcinoma, suitable for either large or small amounts of tumor tissue, did not require specialized equipment and yielded relatively large numbers of viable cells. Cell suspensions prepared by this method could be used to approximate a dose-response curve relating the percentage of tumor takes to the number of cells inoculated and could allow quantitative correlations not possible when macroscopic tumor fragments are used for implantation. The method, or slight modifications of it, should prove suitable for most tissues with a significant connective tissue component.
Abstract 3657: Cross-regulation between the two subsets of NKT cells is dependent on interferon-gamma
Authors: Liat Izhak, Shingo Kato, Stanley T. Parish, Masaki Terabe, Jay A. Berzofsky
Journal: Cancer Research (2014)

Abstract Overcoming the suppression of tumor immunity has been a major challenge in the fight against cancer. Suppression of tumor immunity is being regulated by different kinds of suppressor cells and depleting or blocking their function has been the target of immunotherapy development. One subset of immune suppressors is type II NKT cells. We have previously shown that, upon simultaneous stimulation, type I NKT cells that can promote tumor immunity and type II NKT cells cross regulate each other in vitro as well as in vivo. In some tumor models it was found that activation of type II NKT cells by sulfatide can completely abrogate the protective affect of type I NKT cell activation by alpha-galactosylceramide, leading to tumor progression and reduced survival. However the mechanism for this suppression has not been understood. By co-stimulating NKT cells in vitro, we found that type II NKT cells can inhibit the proliferation of type I NKT cells. By blocking a variety of immunregulators, we found that this suppression is dependent on interferon-gamma (IFNg). Blocking IFNg or its receptor reversed the suppression of type I NKT cell proliferation in vitro. In addition suppression was not observed in IFNgKO C57BL/6 NKT cells. It was also found that exogenous IFNg reduces the proliferation of type I NKT cells after stimulation, suggesting that IFNg is necessary for the suppression of type I NKT cells by type II NKT cells. This was unexpected as IFNg is also an effector cytokine secreted by type I NKT cells. The mechanism is under investigation. Blocking the ability of type II NKT cells to suppress type I NKT cells could shift the balance toward immune protection leading to a better tumor outcome. Citation Format: Liat Izhak, Shingo Kato, Stanley T. Parish, Masaki Terabe, Jay A. Berzofsky. Cross-regulation between the two subsets of NKT cells is dependent on interferon-gamma. [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 3657. doi:10.1158/1538-7445.AM2014-3657
For Debate: Preventing atherosclerotic events with aspirin
Authors: J. G F Cleland
Journal: BMJ (2002)

On p 71 we publish the latest in a series of meta-analyses from the Antithrombotic Trialists' Collaboration.Here John Cleland argues that, despite the vast size of these meta-analyses, the evidence in support of aspirin preventing atherosclerotic events is still inconclusive.One adverse effect of the belief that aspirin is more effective than it is, he argues, is the neglect of more effective drugs for preventing heart disease and stroke.The third meta-analysis from the Antithrombotic Trialists' Collaboration, published in this issue, contains data on over 100 000 patients at high risk of atherosclerotic events, representing more than 250 000 patient years of follow up. 1 This meta-analysis and its predecessors form the major argument for the current widespread fashion of prescribing aspirin to such patients. 2 3It is an enormous body of research and the collaboration is to be congratulated for having gathered so much data.However, quality as well as quantity matters.And the quality is such that the results can only be inconclusive. Trials do not show that aspirin saves livesMeta-analysis is increasingly viewed either as a way of verifying that the outcome of an individual trial is consistent with the rest of the known data or as a way of generating a hypothesis.However, in the absence of a definitively positive trial, many consider meta-analysis inadequate evidence for clinical decision making.4][5][6] Since the benefit from treatment with antiplatelet agents is small, these flaws could lead to erroneous conclusions.It is remarkable-and probably statistically significant-how seldom trials of antiplatelet agents have shown benefit on their selected primary outcome.The choice of the primary endpoint by the Antithrombotic Trialists' Collaboration is arbitrary and suspect.Antiplatelet agents seem to be substantially more effective in reducing the incidence of non-fatal events than in reducing death.Indeed, among large long term trials after myocardial infarction there is no evidence that aspirin saves lives.An intervention can reduce non-fatal events in three ways: by genuinely reducing them, by concealing them, or by converting non-fatal events into fatal ones.The failure of aspirin to reduce mortality despite a reduction in non-fatal events in many studies suggests that aspirin may conceal, rather than prevent, vascular
Two Cows and a Young Bull Beside a Fence in a Meadow
Authors: M. Therese Southgate
Journal: JAMA (2000)

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
Abstract 8298: Cardiac Structure and Function and Mortality in the Oldest Old
Authors: David Leibowitz, Irit Stessman-Lande, Jeremy Jacobs, Aharon Cohen, Eliana Ein-Mor, Jochanan Stessman, Dan Gilon
Journal: Circulation (2011)

Background: People over the age of 85 are the world's most rapidly growing age group and have a high incidence of cardiovascular mortality. The prognostic significance of abnormalities in cardiac structure and function in this age group is unclear. The objective of this study was to prospectively determine the prognosis of abnormal cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920-1921. Methods: Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a portable echocardiograph at the subjects place of residence. Standard echocardiographic assessment of cardiac structure and function was performed. 5-year mortality was assessed via a centralized government database. Results: 502 subjects (235 males, 267 females) were enrolled in the study of whom 107 (21%) died at the time of 5-year follow-up. Subjects who died had significantly higher left atrial volume index (LAVI) (42.3 ± 16.5 mL vs. 36.6 ± 12.5 mL; p &lt; 0.01), and left ventricular mass index (LVMI) (133.1 ± 47.6 vs. 119.8 ± 30.6 g/m2; p &lt; 0.05). Ejection fraction was significantly lower in subjects who died (52.5 ± 11.5% vs. 56.4 ± 9.4%; p &lt; 0.003) however, indices of diastolic function were not significantly different between the two groups (E:e' 13.0 ± 5.3 vs. 12.2 ± 4.9; p = 0.18). these findings remained significant after correction for possible confounders. Conclusions: Elevated LAVI and LVMI and decreased systolic function predict 5-year mortality in a community-dwelling population of the oldest old Diastolic dysfunction did not predict 5-year mortality in this cohort.
INVESTIGATIONS ON EOSINOPHILIA*.
Authors: W. E. PARISH
Journal: British Journal of Dermatology (1970)

SUMMARY.— Eosinophilia in guinea‐pigs and mice is mediated by antibodies that sensitize tissues anaphylactically. In the guinea‐pig these are guinea‐pig γ1 globulin antibodies and rabbit passive sensitizing antibodies; in the mouse, mouse γ1 globulin and reagin. The γ2 globulin antibodies in both species, mediate Arthus reactions without eosinophilia. However, in vitro, there is no difference between eosinophils and neutrophils in their response to antigen‐antibody complexes containing either γ2 or γ1 globulin, which are ingested by both types of cell. Eosinophils in anaphylactic or parasitized tissues are particularly attracted to large, basophilic mononuclear cells which are found in mesenteric milk spots, around parasitic granulomata and probably in lymph nodes. Histamine fails to evoke eosinophilia in guinea‐pigs and rats, though it traps eosinophils in the tissues, forming an apparent eosinophilia. Anti‐histamine drugs fail to suppress the eosinophilia of anaphylaxis in guinea‐pigs. Though generalized or local anaphylaxis results in eosinophilia, it is not known whether complexes of antigen with tissue passive sensitizing antibody on the cell surface attract the eosinophils, or whether they are attracted by some vascular permeability factor released from the anaphylactic cells.
Metabolic Syndrome Recasts Old Cardiac, Diabetes Risk Factors as a "New" Entity
Authors: Mike Mitka
Journal: JAMA (2004)

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
Nasopharyngeal carriage of Streptococcus pneumoniae in children's day-care centers; 10-month follow-up study in Nice, France
Authors: C. Pradier, B. Dunais, R. Largillier, H. Carsenti-Etesse, E. Bernard, A. Scheimberg, P. Dellamonica
Journal: Clinical Microbiology and Infection (1997)
A lesson learnt: The virus and the hookworm
Authors: S. V Ramanan
Journal: BMJ (1999)

Hookworm infestation with the nematode Necator americanus is endemic in the highlands of Sri Lanka. Patients present profoundly anaemic with a characteristic facial appearance that often lends itself to a “spot diagnosis.” Indeed, it was common for an intern to tell a colleague in passing, “I see you've got another hookworm coming in.”

Hepatitis A, or infectious hepatitis as it was known a few decades ago (to distinguish it from hepatitis B or serum hepatitis), was also a common infection. At any time, the medicine ward would include three or four patients so afflicted. As inspection of the urine was a better index of jaundice than examination of the eyes, clear glass jars containing a morning specimen of urine could be seen by each patient's bedside. Then, as now, the treatment was largely supportive. As managed care was …
Drugging the unfolded protein response in acute leukemias
Authors: Behzad Kharabi Masouleh, Eric Chevet, Jens Panse, Edgar Jost, Michael O’Dwyer, Tim H. Bruemmendorf, Afshin Samali
Journal: Journal of Hematology & Oncology (2015)

The unfolded protein response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, is mediated by three major stress sensors IRE-1α, PERK, and ATF6α. Studies described the UPR as a critical network in selection, adaptation, and survival of cancer cells. While previous reviews focused mainly on solid cancer cells, in this review, we summarize the recent findings focusing on acute leukemias. We take into account the impact of the underlying genetic alterations of acute leukemia cells, the leukemia stem cell pool, and provide an outline on the current genetic, clinical, and therapeutic findings. Furthermore, we shed light on the important oncogene-specific regulation of individual UPR signaling branches and the therapeutic relevance of this information to answer the question if the UPR could be an attractive novel target in acute leukemias.
Antilymphocyte globulin, cyclosporin, and granulocyte colony- stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party
Authors: A Bacigalupo, G Broccia, G Corda, W Arcese, M Carotenuto, A Gallamini, F Locatelli, PG Mori, P Saracco, G Todeschini
Journal: Blood (1995)
Abstract P4-11-39: Epithelial-mesenchymal transition phenotype in triple negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome
Authors: Min Hye Jang, Hyun Jeong Kim, Eun Joo Kim, Hee Jin Lee, So Yeon Park
Journal: Cancer Research (2015)

Abstract Background: Triple negative breast cancer (TNBC) is a heterogeneous group of disease. TNBC is closely related to epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotype. Recent studies have shown that TNBC can be classified into six subtypes including basal-like, mesenchymal–like and mesenchymal stem-like. However, clinical significance of EMT phenotype in TNBC is not clear. Methods: We performed immunohistochemical analyses of EMT markers (expression of vimentin, smooth muscle actin, osteonectin and N-cadherin; loss of E-cadherin), BCSC markers (CD44+/CD24- and ALDH1) and EMT inducers (CD146 and ZEB1) in 173 TNBCs using tissue microarrays, and correlated their expressions with clinicopathologic features of the tumor. Results: Expression of vimentin, CD44+/CD24- and CD146 was significantly higher in basal-like TNBCs (TNBC with expression of CK5/6 and/or EGFR) than in non-basal-like TNBCs. Expression of EMT markers was commonly correlated with high histologic grade, CD44+/CD24- phenotype and metaplastic carcinoma. CD146 expression was related to the expression of EMT markers and CD44+/CD24- phenotype. ZEB1 expression showed an association with the expression of smooth muscle actin, but not with BCSC markers. And it was closely correlated with high histologic grade and metaplastic carcinoma. In survival analyses, although expression of EMT and BCSC makers was not associated with the survival of the patients, ZEB1 expression was found to be an independent prognostic factor for poor disease-free survival of the patients. Conclusion: EMT phenotype can be a signature of certain subgroup of TNBC. Especially, ZEB1 expression can be used as a potential biomarker to define a subgroup of TNBC associated with poor clinical outcome. Citation Format: Min Hye Jang, Hyun Jeong Kim, Eun Joo Kim, Hee Jin Lee, So Yeon Park. Epithelial-mesenchymal transition phenotype in triple negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-39.
Trends in the Quality of Care for Medicare Beneficiaries Admitted to the Hospital With Unstable Angina
Authors: Harlan M. Krumholz, Daniel M. Philbin, Yun Wang, Viola Vaccarino, Jaime E. Murillo, Michael L. Therrien, Jeanne Williams, Martha J. Radford
Journal: Journal of the American College of Cardiology (1998)

Objectives. We sought to 1) determine the proportion of appropriate elderly patients admitted to the hospital with unstable angina who are treated with aspirin and heparin; 2) identify patient factors associated with the Agency for Health Care Policy and Research (AHCPR) guideline-based use of aspirin and heparin; and 3) compare practice patterns and patient outcomes before and after publication of the AHCPR guidelines. Background. Improving the care of patients with unstable angina may provide immediate opportunities to mitigate the adverse consequences of unstable angina. However, despite the importance of this diagnosis, there is a paucity of information on the patterns of treatment and outcomes across diverse sites and recent trends in practice that have occurred, especially since the publication of the AHCPR practice guidelines. Methods. We performed a retrospective cohort study using data created from medical charts and administrative files. The sample included 300 consecutive patients admitted to one of three Connecticut hospitals in the period 1993 to 1994 and 150 consecutive patients admitted in 1995 with a principal discharge diagnosis of unstable angina or chest pain. Results. Of the 384 patients ≥65 years old who had no contraindications to aspirin on hospital admission, 276 (72%) received it. Of the 369 patients ≥65 years old who had no contraindications to heparin on admission, 88 (24%) received it. Among the 321 patients ≥65 years old who had no contraindications to aspirin at hospital discharge, 208 (65%) were prescribed it. When 1995 was compared with 1993 to 1994, the use of aspirin (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3 to 4.0) and heparin (OR 2.8, 95% CI 1.6 to 4.9) on hospital admission significantly increased, and the use of aspirin at discharge (OR 1.4, 95% CI 0.8 to 2.4) increased. Concomitantly, there was a significant reduction in 30-day readmission (OR 0.52, 95% CI 0.27 to 0.99). Conclusions. Our results indicate an improvement in the care and outcomes of elderly patients with unstable angina, but there remain opportunities for further improvement.
Serum biomarkers for head and neck cancer by proteomic analysis
Authors: Nejat Dalay, Onur Baykara, Semra Demokan, Nur Buyru
Journal: Clinical Cancer Research (2008)

B42   Head and neck cancer is an important disease comprising a significant proportion of the cancers worldwide with a constant incidence. Although specific molecular changes have been described at present there are no screening tests or biomarkers to detect head and neck cancer at an early stage.  Recently proteomic approaches have emerged as a promising approach for the detection of specific protein expression patterns related with cancer. SELDI-TOF analysis is an innovative proteomic technology for the noninvasive analysis of complex biological samples and serum. In this study we investigated the application of serum SELDI protein profiling to the identification of patients with head and neck cancer.  To screeen for specific markers in the sera of patients with head and neck cancer laser desorption and ionization time of flight mass spectrometry (SELDI) was used. Samples from 90 patients and 30 healthy volunteers were analyzed using the IMAC 30-Cu protein chips capable of metal affinity-based reversible protein binding. Proteomic spactra were generated by mass spectrometry and evaluated statistically to select potential biomarkers. Protein peak identification and cluster analysis were performed using the Express 3.0 biomarker pattern analysis software.  Through differential profiling of serum proteins the range of masses from 2000 - 2000 Da containing the majority of the peaks for analysis. The peak detection software identified an average of 80 peaks in the patient spectrum. Several peaks were found to display significantly different expression levels between the patients and control sera. Among the peak clusters revealing differences we selected two specific clusters as prospective candidate biomarkers in sera of the patients. Highly expression of one peak and underexpression of the other compared to control sera were evaluated in a blind test in terms of the ability to classify a separate group of patients and controls.