tbuckley/cabot-search huggingface dataset:
A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients
Authors: Pedro C. Rodriguez, Xitllaly Popa, Odeth Martínez, Silvia Mendoza, Eduardo Santiesteban, Tatiana Crespo, Rosa M. Amador, Ricardo Fleytas, Soraida C. Acosta, Yanine Otero, Gala N. Romero, Ana de la Torre, Mireysi Cala, Lina Arzuaga, Loisel Vello, Delmairis Reyes, Niurka Futiel, Teresa Sabates, Mauricio Catala, Yoanna I. Flores, Beatriz Garcia, Carmen Viada, Patricia Lorenzo-Luaces, Maria A. Marrero, Liuba Alonso, Jenelin Parra, Nadia Aguilera, Yaisel Pomares, Patricia Sierra, Gryssell Rodríguez, Zaima Mazorra, Agustin Lage, Tania Crombet, Elia Neninger
Journal: Clinical Cancer Research (2016)

EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction.To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care.Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline.Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR.
Use of Job-Exposure Matrix in an Occupational Analysis of Lung and Bladder Cancers on the Basis of Death Certificates
Authors: David Coggon, Brian Pannett, E. Donald Acheson
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Use of Job-Exposure Matrix in an Occupational Analysis of Lung and Bladder Cancers on the Basis of Death Certificates Get access David Coggon, David Coggon Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian Pannett, Brian Pannett Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Donald Acheson E. Donald Acheson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 1, January 1984, Pages 61–65, https://doi.org/10.1093/jnci/72.1.61 Published: 01 January 1984 Article history Received: 08 March 1983 Accepted: 12 August 1983 Published: 01 January 1984
Circulating innate lymphoid cells are differentially regulated in allergic and nonallergic subjects
Authors: Vincent Lombardi, Chloé Beuraud, Catherine Neukirch, Hélène Moussu, Lise Morizur, Stéphane Horiot, Sonia Luce, Erik Wambre, Peter Linsley, Sylvie Chollet-Martin, Véronique Baron-Bodo, Michel Aubier, Philippe Moingeon
Journal: Journal of Allergy and Clinical Immunology (2016)
Survival impact of adjuvant tamoxifen on competing causes of mortality in breast cancer survivors, with analysis of mortality from contralateral breast cancer, cardiovascular events, endometrial cancer, and thromboembolic episodes.
Authors: J Ragaz, A Coldman
Journal: Journal of Clinical Oncology (1998)

PURPOSE This study provides estimates of the effect of tamoxifen treatment on mortality from four conditions known to be affected by tamoxifen in women who survive their breast cancer: contralateral breast cancer, cardiovascular events, endometrial cancer, and thromboembolic events. These estimates are in addition to tamoxifen's impact on primary breast cancer mortality. METHODS The effects of tamoxifen were calculated by the use of the published relative risk (RR) rates of the four conditions as affected by adjuvant tamoxifen and their application to the respective Canadian age-specific mortality rates for the same conditions. The final mortality impact of tamoxifen was expressed as net mortality difference between users and nonusers of tamoxifen. RESULTS At 10 years of follow-up, the sum of avoided deaths (contralateral breast cancer, cardiovascular events) and excess deaths (uterine cancer, thromboembolic episodes) resulted in an overall (net) mortality reduction because of tamoxifen use, with 3 to 41 avoided deaths per 1,000 tamoxifen-treated patients who were 50 to 80 years of age. With the follow-up projected until the age of 90 years, the numbers of avoided late deaths attributed to tamoxifen ranged from 38 to 56 per 1,000 patients. CONCLUSION Our calculations that pertain to late breast cancer survivors indicate that there is a more substantial mortality reduction as a result of deaths avoided from contralateral breast cancer and cardiovascular events, despite the moderately increased mortality from endometrial cancer and thromboembolic episodes. The overall tamoxifen-associated mortality reduction occurs, in different magnitudes, in patients of all ages from 50 to 80 years at diagnosis of the primary breast cancer.
Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1
Authors: Hannah C. Jeffery, Bonnie van Wilgenburg, Ayako Kurioka, Krishan Parekh, Kathryn Stirling, Sheree Roberts, Emma E. Dutton, Stuart Hunter, Daniel Geh, Manjit K. Braitch, Jeremy Rajanayagam, Tariq Iqbal, Thomas Pinkney, Rachel Brown, David R. Withers, David H. Adams, Paul Klenerman, Ye H. Oo
Journal: Journal of Hepatology (2015)

Background & AimsMucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored.MethodsThe phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1.ResultsIntrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEβ7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4β7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17.ConclusionsOur findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future.
IMPS-20COMBINATION THERAPY WITH ANTI-PD-1, ANTI-TIM-3, AND FOCAL RADIATION RESULTS IN REGRESSION OF MURINE GLIOMAS
Authors: Jennifer E. Kim, Mira A. Patel, Antonella Mangraviti, Magda Polanczyk, Eileen S. Kim, Debebe Theodros, Esteban Velarde, Ann Liu, Eric Sankey, Dimitrios Mathios, Christopher M. Jackson, Alessandro Olivi, Phuoc Tran, Charles G. Drake, Betty Tyler, Xiaobu Ye, Henry Brem, Drew M. Pardoll, Michael Lim
Journal: Neuro-Oncology (2015)

INTRODUCTION: Checkpoint molecules like programmed death-1 (PD-1) and T cell immunoglobulin mucin-3 (TIM-3) act as negative regulators of the immune system and can be upregulated in the setting of glioblastoma multiforme (GBM). Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produces long-term survivors in a murine glioma model.1 However, tumor infiltrating lymphocytes can express multiple checkpoints (including TIM-3), and expression of ≥2 checkpoints corresponds to a more exhausted T cell phenotype.2 It was therefore hypothesized that the addition of a second checkpoint-blocking antibody could achieve additive or synergistic antitumor effects. METHODS: C57BL/6 mice were implanted with mouse glioma cell line GL261 transfected with luciferase and randomized into 8 treatment arms: (1) control, (2) SRS, (3) anti-PD-1 antibody, (4) anti-TIM-3 antibody, (5) anti-PD-1 + SRS, (6) anti-TIM-3 + SRS, (7) anti-PD-1 + anti-TIM-3, and (8) anti-PD-1 + anti-TIM-3 + SRS. Overall survival was measured. Brain, cervical lymph nodes, and peripheral blood were harvested on day 21 to assess immune activation. RESULTS: Survival benefits were observed with combined anti-TIM-3 antibody + SRS compared to anti-TIM-3 antibody alone with a median survival (MS) of 69 vs. 25 days and overall survival (OS) of 50% vs. 0%, respectively (p < 0.001 by log-rank Mantel-Cox). Dual blockade with anti-TIM-3 + anti-PD-1 antibody also improved survival compared to TIM-3 blockade alone, (MS of 100 vs. 25 days, OS 60% vs. 0%, respectively, p < 0.05). Notably, OS in the triple therapy group (anti-PD-1 + anti-TIM-3 + SRS) was 100% by day 100 (p < 0.05), a significant improvement compared to all other treatment arms. Flow cytometry of organs harvested on day 21 showed that compared to the dual therapy groups, mice treated with triple therapy had increased tumor infiltration by interferon-gamma+ (IFNg) and tumor necrosis factor-alpha+ (TNFa)-producing CD4+ T cells, as well as IFNg+ CD8+ lymphocytes. CONCLUSIONS: Combining anti-TIM-3 with anti-PD-1 and radiation was synergistic and conferred a significant survival benefit.
Epicutaneous Immunotherapy Using Plasma-Derived Factor VIII Reduces the Inhibitory Immune Response to Therapeutic Factor VIII in Experimental Hemophilia a
Authors: Sébastien Lacroix-Desmazes, Adeline Porcherie, Sandrine Delignat, Mathieu Ing, Pierre-Henri Benhamou, Lucie Mondoulet
Journal: Journal of Allergy and Clinical Immunology (2016)
Influences of Preparedness Knowledge and Beliefs on Household Disaster Preparedness
Authors: Tracy N. Thomas, Michelle Leander-Griffith, Victoria Harp, Joan P. Cioffi
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

In response to concern about strengthening the nation's ability to protect its population and way of life (i.e., security) and ability to adapt and recover from emergencies (i.e., resilience), the President of the United States issued Presidential Policy Directive 8: National Preparedness (PPD-8) (1). Signed on March 30, 2011, PPD-8 is a directive for the U.S. Department of Homeland Security to coordinate a comprehensive campaign across government, private and nonprofit sectors, and individuals to build and sustain national preparedness. Despite efforts by the Federal Emergency Management Agency (FEMA) and other organizations to educate U.S. residents on becoming prepared, growth in specific preparedness behaviors, including actions taken in advance of a disaster to be better prepared to respond to and recover, has been limited (2). In 2012, only 52% of U.S. residents surveyed by FEMA reported having supplies for a disaster (2), a decline from 57% who reported having such supplies in 2009 (3). It is believed that knowledge influences behavior, and that attitudes and beliefs, which are correlated with knowledge, might also influence behavior (4). To determine the association between knowledge and beliefs and household preparedness, CDC analyzed baseline data from Ready CDC, a personal disaster preparedness intervention piloted among Atlanta- and Morgantown-based CDC staff members during 2013–2015. Compared with persons with basic preparedness knowledge, persons with advanced knowledge were more likely to have assembled an emergency kit (44% versus 17%), developed a written household disaster plan (9% versus 4%), and received county emergency alert notifications (63% versus 41%). Similarly, differences in household preparedness behaviors were correlated with beliefs about preparedness. Persons identified as having strong beliefs in the effectiveness of disaster preparedness engaged in preparedness behaviors at levels 7%–30% higher than those with weaker preparedness beliefs. Understanding the influences of knowledge and beliefs on household disaster preparedness might provide an opportunity to inform messages promoting household preparedness.
Epstein-Barr Virus in Nasal Lymphomas Contains Multiple Ongoing Mutations in the EBNA-1 Gene
Authors: M.I. Gutiérrez, G. Spangler, D. Kingma, M. Raffeld, I. Guerrero, O. Misad, E.S. Jaffe, I.T. Magrath, K. Bhatia
Journal: Blood (1998)
Nitinol stent insertion in tracheomalacia
Authors: Carmen Pizarro, Darius Dabir, Georg Nickenig, Dirk Skowasch
Journal: Thorax (2016)

A 69-year-old man was admitted to our hospital with progressive dyspnoea accompanied by inspiratory stridor. He presented a history of surgical aortic valve replacement 3 years previously, complicated by prolonged postoperative mechanical ventilation requiring percutaneous tracheostomy. Presently, bronchoscopy evidenced tracheomalacia (TM) with subtotal tracheal stenosis. CT scan confirmed long segment narrowing >20 mm of the upper trachea (figure 1). Operative retracheostomy resulted in repeated tube dislocation …
Endogenous sex hormones and cardiovascular disease in postmenopausal women
Authors: P. Muti, M. Trevisan
Journal: BMJ (1996)

the requirements of journals.The first would obviously be "adverse drug reaction," followed by the nature of the reaction (and if necessary the organ affected when this is not obvious from the wording of the nature of the reaction) and by the generic name of the suspected drug.Optional key words could be the chemical or therapeutic class and the mechanism.An example is "adverse drug reaction, skin, urticaria, ampicillin, ,-lactamines, hypersensitivity."Standardised coding would greatly facilitate the retrieval of information on drug reactions by prescribers, pharmaceutical companies, and anyone else with an interest in the subject.
Prediction of response to chemoradiation in rectal cancer by gene polymorphism and plasma homocysteine
Authors: A. K. Jakobsen, J. N. Nielsen, J. P. Mortensen, A. V. Schmedes, I. Brandslund, J. Lindebjerg
Journal: Journal of Clinical Oncology (2005)

3562 Background: Concurrent chemotherapy and radiation is standard treatment of patients with locally advanced rectal cancer. Most patients have only limited effect and there is an obvious need for new predictive markers to select patients on a rational basis. The aim of the present study was to investigate the predictive value of plasma homocysteine and gene polymorphism to the effect of chemoradiation in patients with advanced T3 rectal cancer. Methods: The study was a phase II trial including 50 patients with a T3 rectal cancer and a close circumferential margin on the MRI scan. All patients received external radiation (60 Gy) with an additional intraluminal boost (5 Gy) and concomittant chemotherapy (UFT 300 mg/m2 daily). Homocysteine was measured in plasma together with B12 and methylmalonic acid before start of treatment. Thymidylate synthase enhancer polymorphism was analyzed in mononuclear cells by PCR technique. The end point was complete pathological remission (CPR) as estimated by histopathological examination of surgical specimens obtained at the operation eight weeks after end of treatment. Results: The overall rate of CPR was 27% but differed according to homocysteine level. The mean value in patients with CPR was 6.4 μ mol/l versus 8.2 μ mol/l in non-CPR patients (p=0.007). No CPR was seen in patients with values > 8.8 μ mol/l. The TS enhancer polymorphism was also correlated with CPR. TS enhancer polymorphism was 54% in patients with a double repeat of 28 base pairs (2R/2R) compared to 25% in the two other groups (2R/3R, 3R/3R). The difference was significant (p=0.007). The combination of plasma homocysteine and TS polymorphism identified a subgroup of patients with a CPR rate of 84%. Conclusions: Plasma homocysteine and TS enhancer polymorphism contain considerable predictive information and can be used to delineate a subgroup of patients having a high chance of CPR by concurrent chemoradiation. The issue calls for further clarification in prospective trials with larger numbers of patients. No significant financial relationships to disclose.
Early Results of a Phase II Study of Ofatumumab As Front-Line Treatment in Elderly, Unfit Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Maria Ciccone, Candida Vitale, Christina Hinojosa, Michael J Keating, Naveen Pemmaraju, Susan O'Brien, Jan A. Burger, Deborah A. Thomas, Hagop M. Kantarjian, Paolo Strati, William G. Wierda, Alessandra Ferrajoli
Journal: Blood (2014)
Evaluation of the efficacy and E2, LH, FSH level when goserelin is used as neoadjuvant therapy with CEF chemotherapy in hormone-responsive and premenopausal breast cancer.
Authors: S. Zhang, J. J. Liu, J. Zhang
Journal: Journal of Clinical Oncology (2010)

e11056 Background: To evaluate the efficacy and E2,LH,FSH level of goserelin combined with CEF chemotherapy as neoadjuvant therapy in hormone responsive, premenopausal, operable breast cancer patients. Methods: Goserelin was administered for 3 cycles with concurrent CEF was given 4 cycles as neoadjuvant therapy. The primary objective was PCR in the breast. The secondary objectives included CR, PR, ORR, change of hormone level pre- and posttherapy, change of biological marker status (ER, PR, HER-2) pre- and posttherapy. Results: 31 patients (26.1%) achieved clinical CR and 76 patients (63.9%) achieved clinical PR; the ORR was 90.0%. 14 patients (11.8%) achieved PCR. When stratified by the clinical lymph node status, the clinical PR rate in clinical lymph node- negative group was significantly better than clinical lymph node-positive group (p = 0.02). When stratified by the hormonal status, the clinical PR rate in ER+PR+ group was significantly better than ER+PR- and ER-PR+ group (p = 0.0471). Hormonal receptor became negative posttherapy in 11 patients (9.2%), whose clinical response rate was significantly lower compared with the posttherapy hormonal receptor positive group (p < 0.001). 109 (91.6%) patients achieved amenorrhea after the first cycle of goserelin, 10 (8.4%) patients achieved amenorrhea after the second cycle of goserelin.The mean level of estrogen was 129.75 ± 88.45 ng/L pretherapy and was 14.04 ± 8.33 ng/L posttherapy. 86.0% patients have their menstruation retrieved within 1-year follow-up. Conclusions: Goserelin combined with CEF chemotherapy as neoadjuvant therapy in hormone responsive, premenopausal breast cancer patients was more effective than CEF chemotherapy alone. This regimen was most effective especially in the clinical lymph node-negative group and ER/PR double-positive group. The clinical response rate will be lower if the hormonal receptor became negative after therapy. This regimen can induce amenorrhea effectively and retrieve menstruation in short time, this result may indicate that goserelin has the potential function against the ovarian function failure caused by chemotherapy. No significant financial relationships to disclose.
Abstract 15249: A Text Messaging Intervention Improves Medication Adherence for Patients With Coronary Heart Disease: A Randomized Controlled Trial
Authors: Linda G. Park, Jill Howie-Esquivel, Misook Chung, Kathleen Dracup
Journal: Circulation (2013)

Introduction: More than half of individuals with chronic diseases do not take medications as prescribed. Pharmacologic treatment for secondary prevention of coronary heart disease (CHD) is critical...
New Treatment for Liposarcoma
Authors: Rebecca Voelker
Journal: JAMA (2016)

The chemotherapy drug eribulin mesylate has received approval for treating liposarcoma that is unresectable or has metastasized (http://1.usa.gov/1ZWmPRo). Marketed as Halaven, the drug is approved for patients previously treated with chemotherapy that contained an anthracycline drug.
Homer Smith Award. Cellular mechanisms in proximal tubular Pi reabsorption
Authors: H Murer
Journal: Journal of the American Society of Nephrology (1992)

Inorganic phosphate (Pi) is reabsorbed mainly in the proximal tubule, by a second active Na-dependent transport mechanism. Na/Pi cotransport with a stoichiometry exceeding unity mediates uphill flux across the brush border membrane; at the basolateral cell surface, two separate transport systems are involved in equilibrating Pi fluxes. The protein structure of a rabbit renal cortex Na/Pi cotransport system has been identified recently by expression cloning. The regulation of tubular Pi reabsorption involves mainly alterations in the transport rate of the brush border membrane Na/Pi cotransport system. The regulation of this transport step by either parathyroid hormone (PTH) or Pi deprivation is discussed, mostly on the basis of observations made with a tissue culture model, OK cells derived from opossum kidney. In this model, PTH may use a dual signaling cascade to inhibit apical Na/Pi cotransport (phospholipase C/protein kinase C and adenylate cyclase/protein kinase A). PTH action on Na/Pi cotransport may involve an endocytosis mechanism. For the regulation of apical Na/Pi cotransport by chronic Pi deprivation, the number of "Na/Pi cotransporter" molecules seems to be unaffected; the increased transport rate is apparently related to an "unknown" stimulating event at the membrane level (e.g., a change in the lipid microenvironment), which itself is under the control of protein synthesis/degradation. The availability of new tools (cloning of Na/Pi cotransporter(s) and of PTH receptor(s)) will allow us to enter into a new era in the study of cellular mechanisms involved in proximal tubular Pi reabsorption.
Infants with acute lymphoblastic leukemia: no evidence for high methotrexate resistance
Authors: NL Ramakers-van Woerden, R Pieters, MG Rots, CH van Zantwijk, P Noordhuis, HB Beverloo, GJ Peters, ER van Wering, BM Camitta, C-H Pui, MV Relling, WE Evans, AJP Veerman
Journal: Leukemia (2002)