tbuckley/cabot-search huggingface dataset:
Treatment of nasopharyngeal carcinoma with human leukocyte interferon.
Authors: J M Connors, W A Andiman, C B Howarth, E Liu, T C Merigan, M E Savage, C Jacobs
Journal: Journal of Clinical Oncology (1985)

Nasopharyngeal carcinoma (NPC) is a human neoplasm closely associated with Epstein-Barr virus (EBV). Human leukocyte interferon (IFN) has known antiviral and antineoplastic properties. After initial IFN treatment in one NPC patient demonstrated acceptably low toxicity, 12 additional patients were treated on a protocol with IFN, 10 X 10(6) units intramuscularly (IM) daily for 30 days. IFN did not affect serum anti-EBV antibody titers (IgA and IgG antiviral capsid and early antigens). Of six patients tested, none was found to excrete EBV in saliva before, during, or after IFN. Four patients had measurable tumor regression (two partial responses and two minor responses), three had stable disease, and five patients plus the initial preprotocol patient had progressive disease. Toxicity included fever, fatigue, and myalgias in all patients, thrombocytopenia in two patients, and neutropenia in three patients. Three patients were withdrawn from the study, one each for severe fatigue, neutropenia, and hypotension. This study demonstrates that IFN has sufficient activity in advanced NPC to justify further investigation.
Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease
Authors: Nicolaus Kröger, Carlos Solano, Christine Wolschke, Giuseppe Bandini, Francesca Patriarca, Massimo Pini, Arnon Nagler, Carmine Selleri, Antonio Risitano, Giuseppe Messina, Wolfgang Bethge, Jaime Pérez de Oteiza, Rafael Duarte, Angelo Michele Carella, Michele Cimminiello, Stefano Guidi, Jürgen Finke, Nicola Mordini, Christelle Ferra, Jorge Sierra, Domenico Russo, Mario Petrini, Giuseppe Milone, Fabio Benedetti, Marion Heinzelmann, Domenico Pastore, Manuel Jurado, Elisabetta Terruzzi, Franco Narni, Andreas Völp, Francis Ayuk, Tapani Ruutu, Francesca Bonifazi
Journal: New England Journal of Medicine (2016)

Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling.We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease.After a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P<0.001). The rate of 2-year relapse-free survival was similar in the ATG group and the non-ATG group (59.4% [95% CI, 47.8 to 69.2] and 64.6% [95% CI, 50.9 to 75.3], respectively; P=0.21), as was the rate of overall survival (74.1% [95% CI, 62.7 to 82.5] and 77.9% [95% CI, 66.1 to 86.1], respectively; P=0.46). There were no significant between-group differences in the rates of relapse, infectious complications, acute GVHD, or adverse events. The rate of a composite end point of chronic GVHD-free and relapse-free survival at 2 years was significantly higher in the ATG group than in the non-ATG group (36.6% vs. 16.8%, P=0.005).The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point of chronic GVHD-free survival and relapse-free survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.).
Authors' response
Authors: K S Boparai, J B Reitsma, E Dekker
Journal: Gut (2011)

Patients with hyperplastic polyposis syndrome (HPS) harbour multiple colorectal hyperplastic polyps and are at risk of developing colorectal cancer (CRC).1 2 In two recent studies from our study group, we described the risk of CRC in patients with HPS during follow-up and the RR of CRC/polyps in first-degree relatives (FDRs) of patients with HPS compared to the general population.1 2 In reaction to our manuscripts, Orlowska3 recommends that a distinction be made between sessile serrated adenomas and traditional serrated adenomas. We agree with this remark, considering that these serrated polyp subtypes differ in histological and geographical characteristics and in molecular profiles.4 Considering that both studies from our group involved …
Abstract 15141: Usefulness of New Parameters Based on Frank-Starling Mechanism for Systolic and Diastolic Dysfunction in Atrial Fibrillation
Authors: Chee Jeong Kim, Wang-Soo Lee, Kwang Je Lee, Sang-Wook Kim, Tae Ho Kim
Journal: Circulation (2012)

Introduction: The role of Frank-Starling mechanism is well established in systolic left ventricular (LV) function. Irregular RR intervals in atrial fibrillation (AF) provide the opportunity for cli...
Corrigendum to “Optically guided controlled release from liposomes with tunable plasmonic nanobubbles” [J. Control. Release, 2010, 144, 151–158]
Authors: Lindsey J.E. Anderson, Eric Hansen, Ekaterina Y. Lukianova-Hleb, Jason H. Hafner, Dmitri O. Lapotko
Journal: Journal of Controlled Release (2016)
Abstract 11175: Public Access Defibrillation Improved the Outcome after Out-Of-Hospital Cardiac Arrests in School-Age Children: A Nationwide, Population-Based, Utstein Registry Study in Japan
Authors: Yoshihide Mitani, Kunio Ohta, Noriko Yodoya, Shoichiro Otsuki, Hiroyuki Ohashi, Hirofumi Sawada, Masami Nagashima, Naokata Sumitomo, Yoshihiro Komada
Journal: Circulation (2012)

Introduction: Since the lay use of automated external defibrillator (AED) was approved in Japan in 2004, the number of AED devices in public locations increased to 203,924 (106.6/100,000 population...
Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response
Authors: Andrew R. Conery, Richard C. Centore, Kerry L. Spillane, Nicole E. Follmer, Archana Bommi-Reddy, Charlie Hatton, Barbara M. Bryant, Patricia Greninger, Arnaud Amzallag, Cyril H. Benes, Jennifer A. Mertz, Robert J. Sims
Journal: Cancer Research (2016)

Small-molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are being tested in clinical trials for a variety of cancers, but patient selection strategies remain limited. This challenge is partly attributed to the heterogeneous responses elicited by BET inhibition (BETi), including cellular differentiation, senescence, and death. In this study, we performed phenotypic and gene-expression analyses of treatment-naive and engineered tolerant cell lines representing human melanoma and leukemia to elucidate the dominant features defining response to BETi. We found that de novo and acquired tolerance to BETi is driven by the robustness of the apoptotic response, and that genetic or pharmacologic manipulation of the apoptotic signaling network can modify the phenotypic response to BETi. We further reveal that the expression signatures of the apoptotic genes BCL2, BCL2L1, and BAD significantly predict response to BETi. Taken together, our findings highlight the apoptotic program as a determinant of response to BETi, and provide a molecular basis for patient stratification and combination therapy development.
Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line
Authors: Deepti Chopra, Lipika Ray, Ashish Dwivedi, Shashi Kant Tiwari, Jyoti Singh, Krishna P. Singh, Hari Narayan Kushwaha, Sadaf Jahan, Ankita Pandey, Shailendra K. Gupta, Rajnish Kumar Chaturvedi, Aditya Bhushan Pant, Ratan Singh Ray, Kailash Chand Gupta
Journal: Biomaterials (2016)
Effects of socioeconomic and clinical factors on survival in multiple myeloma.
Authors: B Weston, S Grufferman, J P MacMillan, H J Cohen
Journal: Journal of Clinical Oncology (1987)

It was recently reported that low socioeconomic status (SES) in multiple myeloma (MM) patients is associated with a poorer prognosis. To reassess this finding in another group of MM patients, we used data from interviews of 153 MM patients seen at Duke University Medical Center over a 6-year period. Medical records were also reviewed for data on traditional clinical prognostic factors. Using proportional hazard survival analysis, no SES variables were associated with survival. Current income, highest income, occupation, type of dwelling, years of education, and crowding did not enter the stepwise regression model at alpha = .10. In contrast, many clinical factors predicted prognosis (calcium, P = .019; percent plasma cells on initial bone marrow, P = .019; history of transfusions, P = .015; WBC count, P = .007; pathologic fractures, P = .001; and urate, P less than .001). Thus, we do not confirm the previously reported association between social class and myeloma survival.
Roles of Periostin in Respiratory Disorders
Authors: Kenji Izuhara, Simon J. Conway, Bethany B. Moore, Hisako Matsumoto, Cecile T. J. Holweg, John G. Matthews, Joseph R. Arron
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Periostin is a matricellular protein that has been implicated in many disease states. It interacts with multiple signaling cascades to modulate the expression of downstream genes that regulate cellular interactions within the extracellular matrix. This review focuses on the role of periostin in respiratory diseases, including asthma and idiopathic pulmonary fibrosis, and its potential to help guide treatment or assess prognosis. Epithelial injury is a common feature of many respiratory diseases, resulting in the secretion, among others, of periostin, which is subsequently involved in airway remodeling and other aspects of pulmonary pathophysiology. In asthma, periostin is recognized as a biomarker of type 2 inflammation; POSTN gene expression is up-regulated in bronchial epithelial cells by IL-13 and IL-4. Serum periostin has been evaluated for the identification of patients with increased clinical benefit from treatment with anti-IL-13 (lebrikizumab, tralokinumab) and anti-IgE (omalizumab) therapy and may be prognostic for increased risk of asthma exacerbations and progressive lung function decline. Furthermore, in asthma, periostin may regulate subepithelial fibrosis and mucus production and may serve as a systemic biomarker of eosinophilic airway inflammation. Periostin is also highly expressed in the lungs of patients with idiopathic pulmonary fibrosis, and its serum levels may predict clinical progression. Overall, periostin contributes to multiple pathogenic processes across respiratory diseases, and peripheral blood levels of periostin may have utility as a biomarker of treatment response and disease progression.
For What?
Authors: L Stewart Massad
Journal: JAMA (2003)

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
Chronic dexamethasone treatment results in resistance, IL6-independence, and altered JAK/STAT signaling in the 7TD1 murine B cell hybridoma.
Authors: Kalyan J. Gangavarapu, Sandi Pearce, Jeremy Ebrahimpour, Tsedey Kassaye Betre, Christopher K. Daniels
Journal: Cancer Research (2006)

5092  Multiple myeloma is a B cell malignancy with poor prognosis. Interleukin-6 (IL-6) is an important cytokine growth factor for the proliferation of multiple myeloma cells in the early stages of the disease. JAK/STAT3 signaling, triggered by IL-6, promotes proliferation and survival of myeloma cells. In the later stages of the disease, myeloma cells begin proliferating independent of IL-6 and develop resistance on chronic treatment with chemotherapy agents like dexamethasone. Using the IL-6 dependent murine B hybridoma cell line, 7TD1, as a model for IL-6 dependent multiple myeloma cells, our aim was to investigate and characterize the response of 7TD1 cells to chronic dexamethasone treatment. Chronic treatment with dexamethasone (85uM) resulted in a cell population (7TD1 Dxm), which was resistant to dexamethasone induction of apoptosis and inhibition of proliferation. These cells were cross-resistant to melphalan and thalidomide, but not etoposide. In addition to resistance, at this stage they also show IL-6 independent growth. Inhibition of proliferation by an IL-6 neutralizing antibody suggests that they may be producing and utilizing IL-6. Results from western blotting suggest that STAT3 phosphorylation observed only in the presence of IL-6 in parent 7TD1 cells also showed inhibition by the JAK inhibitor AG490 (50uM). On the other hand, 7TD1Dxm cells showed constitutive activation of STAT3 and resistance to AG490 inhibition and apoptosis. These results suggest an altered JAK/STAT3 signaling in chronically treated cells. In addition, treatment with AG490 did not alter resistance of chronically treated cells to dexamethasone. Further investigations to look at IL-6 gene expression and IL-6 signaling pathways in chronically treated 7TD1 cells may be helpful in finding potential targets which may inhibit progression of multiple myeloma. This work was partially supported by NIH Grant # P20 RR016454 from the INBRE Program of the National Center for Research Resources
Therapy for Older AML Patients: The Role of Novel Agents and Allogeneic Stem Cell Transplant
Authors: Jeffrey E. Lancet, Sergio Giralt
Journal: Journal of the National Comprehensive Cancer Network (2008)

The development of novel therapeutics in acute myeloid leukemia (AML) is driven by the need to improve efficacy and reduce toxicity. Clearly, elderly patients with AML represent a highly heterogeneous group, based on a wide array of disease- and patient-specific characteristics. Therefore, novel treatment strategies aimed at overcoming specific biologic modifiers of disease resistance will be paramount to successful therapy for some, whereas in others, the ability to administer a low-toxicity regimen on a chronic basis to achieve disease control may prove beneficial, perhaps even in the absence of complete responses. In addition, identifying genomic and proteomic expression patterns using an individual's unique neoplastic clone will likely optimize the ability to predict responders to novel therapies and identify new and relevant therapeutic targets. The development of reduced-intensity preparative regimens for allogeneic transplants has allowed physicians and patients to explore the option of long-term disease control. The risk–benefit ratio for this procedure will depend on the disease state, patient performance status, and comorbidities. However, current results underscore that age alone should no longer be a contraindication for allogeneic transplant with curative intent in these patients, and long-term disease control with good quality of life is possible and can be expected. Future trials combining the novel therapies described in this article and novel transplant technologies should allow more elderly patients with AML or myelodysplastic syndromes to experience long and productive lives.
Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires
Authors: David Burstein, Francisco Amaro, Tal Zusman, Ziv Lifshitz, Ofir Cohen, Jack A Gilbert, Tal Pupko, Howard A Shuman, Gil Segal
Journal: Nature Genetics (2016)

Gil Segal, Howard Shuman and colleagues sequence the genomes of 38 Legionella species and analyze 5,885 predicted effector proteins. Their analysis identifies a core set of seven effectors shared by all 38 species and numerous previously unidentified conserved effector domains. Infection by the human pathogen Legionella pneumophila relies on the translocation of ∼300 virulence proteins, termed effectors, which manipulate host cell processes. However, almost no information exists regarding effectors in other Legionella pathogens. Here we sequenced, assembled and characterized the genomes of 38 Legionella species and predicted their effector repertoires using a previously validated machine learning approach. This analysis identified 5,885 predicted effectors. The effector repertoires of different Legionella species were found to be largely non-overlapping, and only seven core effectors were shared by all species studied. Species-specific effectors had atypically low GC content, suggesting exogenous acquisition, possibly from the natural protozoan hosts of these species. Furthermore, we detected numerous new conserved effector domains and discovered new domain combinations, which allowed the inference of as yet undescribed effector functions. The effector collection and network of domain architectures described here can serve as a roadmap for future studies of effector function and evolution.
Study of Cardiovascular Health Outcomes in the Era of Claims Data
Authors: Bruce M. Psaty, Joseph A. Delaney, Alice M. Arnold, Lesley H. Curtis, Annette L. Fitzpatrick, Susan R. Heckbert, Barbara McKnight, Diane Ives, John S. Gottdiener, Lewis H. Kuller, W.T. Longstreth
Journal: Circulation (2015)

Background— Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. Methods and Results— Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare &amp; Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI. Conclusions— The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.
Relationship Between Major Vault Protein/Lung Resistance Protein, Multidrug Resistance-Associated Protein, P-Glycoprotein Expression, and Drug Resistance in Childhood Leukemia
Authors: M.L. den Boer, R. Pieters, K.M. Kazemier, M.M.A. Rottier, C.M. Zwaan, G.J.L. Kaspers, G. Janka-Schaub, G. Henze, U. Creutzig, R.J. Scheper, A.J.P. Veerman
Journal: Blood (1998)
Nominations open for eighth annual BMJ Awards
Authors: Nigel Hawkes
Journal: BMJ (2015)

The search for medical excellence is on again as The BMJ Awards 2016 invite nominations for the eighth year of a competition now firmly established in the annual medical calendar. The process that begins with completing a nomination form could end for the winners in recognition among their peers at a gala night at the Park Plaza Hotel on Westminster Bridge Road, London, on 5 May, when the awards will be presented.

The format is firmly established and a proven success, but each year sees evolutionary changes designed to ensure that it targets the right areas of medicine in the right way. This year’s most significant change is the introduction of expert patients in the judging process—each panel will include at least one patient, in keeping with The BMJ ’s Patient Partnership initiative (bmj.com/campaign/patient-partnership), launched last year.

Once again, the headline sponsor for the awards is MDDUS, the Medical and Dental …
Phase II trial of levocetirizine with capecitabine and bevacizumab to overcome the resistance of antiangiogenic therapies in refractory metastatic colorectal cancer.
Authors: Manik Amin, Monica Dandona Desai, Steven Sorscher, Kian-Huat Lim, Andrea Wang-Gillam, Benjamin R. Tan, Joel Picus, Maureen Highkin, Kimberly Lears, Albert C. Lockhart
Journal: Journal of Clinical Oncology (2015)

763 Background: Despite clinical success of VEGF blockade in mCRC, resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in resistance development to anti-angiogenic therapy. Levocetirizine is a third generation antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850mg/m 2 – 7 days on and 7 days off, IV bevacizumab 5 mg/kg every 14 days and oral levocetirizine 5 mg daily in 14 day cycles. The primary end point was PFS and secondary endpoints included ORR and tolerability. An exploratory endpoint included correlation of PFS with cytokine (IL-8 &amp; IL-6) levels. A sample size of 36 evaluable patients could identify a median PFS of 3.4 months at a 0.05 significance level. To document cytokine changes related to levocetirizine treatment, patients were randomized to Arm A where levocetirizine was started 7 days after starting chemotherapy or to Arm B where levocetirizine was started 7 days prior to chemotherapy. For PFS determination both arms were combined for analysis. Cytokine levels were measured at baseline and with each cycle of chemotherapy (up to three cycles). Results: 43 patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 20 patients and Arm B enrolled 23 patients. Of the patients evaluable for best response, 19 had SD and 12 had PD. Median PFS of all patients on the study was 3.4 months (ranging 0.9 to 10.6 months). Conclusions: Median PFS in the trial was comparable to and possibly better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine analysis is in progress and these results and correlations with patient outcomes will be presented to assess the impact of cytokine blockade on mCRC treatment. Clinical trial information: NCT01722162.