Detection of p73 antibodies in patients with various types of cancer: immunological characterization

p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino- and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells. © 2001 Cancer Research Campaign http://www.bjcancer.co

Normal families and fixed points of iterates

Let F be a family of holomorphic functions and let K be a constant less than 4. Suppose that for all f in F the second iterate of f does not have fixed points for which the modulus of the multiplier is greater than K. We show that then F is normal. This is deduced from a result about the multipliers of iterated polynomials.Comment: 5 page

derived neutrophil to lymphocyte ratio dnlr change between baseline and cycle 2 is correlated with benefit during immune checkpoint inhibitors ici in advanced non small cell lung cancer nsclc patients

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Risk of malignant lymphoma associated with human herpesvirus-8: a case–control study in Spain

No overall increased risk of lymphoma associated with antibodies to human herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19 lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73)

Lyapunov exponents, bifurcation currents and laminations in bifurcation loci

Bifurcation loci in the moduli space of degree $d$ rational maps are shaped by the hypersurfaces defined by the existence of a cycle of period $n$ and multiplier 0 or $e^{i\theta}$. Using potential-theoretic arguments, we establish two equidistribution properties for these hypersurfaces with respect to the bifurcation current. To this purpose we first establish approximation formulas for the Lyapunov function. In degree $d=2$, this allows us to build holomorphic motions and show that the bifurcation locus has a lamination structure in the regions where an attracting basin of fixed period exists

Is the perceived neighborhood built environment associated with domain-specific physical activity in Latin American adults? An eight-country observational study

© The Author(s). 2020 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Characteristics of the neighborhood built environment are associated with physical activity (PA). However, few studies with representative samples have examined environmental correlates of domain-specific PA in Latin America. We examined the associations of the perceived neighborhood built environment with domain-specific PA in a large sample of adults from eight Latin American countries. Methods: This study examined data from 8185 adults (aged 18–65 years) from eight Latin American countries. The Neighbourhood Environment Walkability Survey - Abbreviated (NEWS-A) scale was used to assess perceptions of land use mix–diversity, land use mix-access, street connectivity, walking/cycling facilities, aesthetics, safety from traffic, and safety from crime. Perceived proximity from home to public open spaces (metropolitan parks, playgrounds, public squares) and to shopping centers was also measured. Transport-related and leisure-time PA were assessed using the long form of the International Physical Activity Questionnaire. Both logistic and linear regression models were estimated on pooled data. Results: Perceptions of higher land use mix-access (OR: 1.40; 95% CI: 1.22,1.61), the existence of many alternative routes in the neighbourhood (1.12; 1.04,1.20), slow speed of traffic (1.19; 1.03,1.35) and few drivers exceeding the speed limits (1.09; 1.03,1.15) were associated with greater odds of reporting at least 10 min/week of transport-related PA. Perceptions of higher levels of land use mix-diversity, better aesthetics and greater safety from crime, the presence of crosswalks and pedestrian signals, and greater proximity of shopping centers were associated with more min/week of transport-related PA. Perceptions of higher land use mix-diversity (1.12; 1.05,1.20), higher land use mix-access (1.27; 1.13,1.43), more walking/cycling facilities (1.18; 1.09,1.28), and better aesthetics (1.10; 1.02,1.18) were associated with greater odds of engaging in at least 10 min/week of leisure-time PA versus none. Perceptions of higher land use mix-diversity were associated with more min/week of leisure PA. Conclusions: Different perceived neighborhood built environment characteristics were associated with domain-specific PA among adults from Latin America countries. Interventions designed to modify perceptions of the neighbourhood built environment might influence initiation or maintenance of domain-specific PA.Fieldwork and data analysis compromised in ELANS protocol was supported by a scientific grant from the Coca Cola Company, and by grant and/ or support from Instituto Pensi/Hospital Infantil Sabara, International Life Science Institute of Argentina, Universidad de Costa Rica, Pontificia Universidad Católica de Chile, Pontificia Universidad Javeriana, Universidad Central de Venezuela (CENDES-UCV)/Fundación Bengoa, Universidad San Francisco de Quito, and Instituto de Investigación Nutricional de Peru. André Werneck is supported by the São Paulo Research Foundation (FAPESP) with a PhD scholarship (FAPESP process: 2019/24124–7). This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. The funding sponsors had no role in study design; the collection, analyses, or interpretation of data; writing of the manuscript; or in the decision to publish the results.info:eu-repo/semantics/publishedVersio

CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK