Carcinogenicity assessment: Addressing the challenges of cancer and chemicals in the environment.
Ontology highlight
ABSTRACT:
SUBMITTER: Madia F
PROVIDER: S-EPMC6520474 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Carcinogenicity assessment: Addressing the challenges of cancer and chemicals in the environment.
Madia Federica F Worth Andrew A Whelan Maurice M Corvi Raffaella R
Environment international 20190509
Cancer is a key public health concern, being the second leading cause of worldwide morbidity and mortality after cardiovascular diseases. At the global level, cancer prevalence, incidence and mortality rates are increasing. These trends are not fully explained by a growing and ageing population: with marked regional and socioeconomic disparities, lifestyle factors, the resources dedicated to preventive medicine, and the occupational and environmental control of hazardous chemicals all playing a ...[more]
Similar Datasets
Project description:In view of the need to enhance the assessment of consumer products called for in the EU Chemicals Strategy for Sustainability, we developed a methodology for evaluating hazard by combining information across different systemic toxicity endpoints and integrating the information with new approach methodologies. This integrates mechanistic information with a view to avoiding redundant in vivo studies, minimising reliance on apical endpoint tests and ultimately devising efficient testing strategies. Here, we present the application of our methodology to carcinogenicity assessment, mapping the available information from toxicity test methods across endpoints to the key characteristics of carcinogens. Test methods are deconstructed to allow the information they provide to be organised in a systematic way, enabling the description of the toxicity mechanisms leading to the adverse outcome. This integrated approach provides a flexible and resource-efficient means of fully exploiting test methods for which test guidelines are available to fulfil regulatory requirements for systemic toxicity assessment as well as identifying where new methods can be integrated.
| S-EPMC8166685 | biostudies-literature
Project description:Currently, there are >11,000 synthetic turf athletic fields in the United States and >13,000 in Europe. Concerns have been raised about exposure to carcinogenic chemicals resulting from contact with synthetic turf fields, particularly the infill material ("crumb rubber"), which is commonly fabricated from recycled tires. However, exposure data are scant, and the limited existing exposure studies have focused on a small subset of crumb rubber components. Our objective was to evaluate the carcinogenic potential of a broad range of chemical components of crumb rubber infill using computational toxicology and regulatory agency classifications from the United States Environmental Protection Agency (US EPA) and European Chemicals Agency (ECHA) to inform future exposure studies and risk analyses. Through a literature review, we identified 306 chemical constituents of crumb rubber infill from 20 publications. Utilizing ADMET Predictor™, a computational program to predict carcinogenicity and genotoxicity, 197 of the identified 306 chemicals met our a priori carcinogenicity criteria. Of these, 52 chemicals were also classified as known, presumed or suspected carcinogens by the US EPA and ECHA. Of the remaining 109 chemicals which were not predicted to be carcinogenic by our computational toxicology analysis, only 6 chemicals were classified as presumed or suspected human carcinogens by US EPA or ECHA. Importantly, the majority of crumb rubber constituents were not listed in the US EPA (n?=?207) and ECHA (n?=?262) databases, likely due to an absence of evaluation or insufficient information for a reliable carcinogenicity classification. By employing a cancer hazard scoring system to the chemicals which were predicted and classified by the computational analysis and government databases, several high priority carcinogens were identified, including benzene, benzidine, benzo(a)pyrene, trichloroethylene and vinyl chloride. Our findings demonstrate that computational toxicology assessment in conjunction with government classifications can be used to prioritize hazardous chemicals for future exposure monitoring studies for users of synthetic turf fields. This approach could be extended to other compounds or toxicity endpoints.
| S-EPMC6396308 | biostudies-literature
Project description:Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.
| S-EPMC1131930 | biostudies-literature
Project description:Over 300 million arthropod specimens are housed in North American natural history collections. These collections represent a "vast hidden treasure trove" of biodiversity -95% of the specimen label data have yet to be transcribed for research, and less than 2% of the specimens have been imaged. Specimen labels contain crucial information to determine species distributions over time and are essential for understanding patterns of ecology and evolution, which will help assess the growing biodiversity crisis driven by global change impacts. Specimen images offer indispensable insight and data for analyses of traits, and ecological and phylogenetic patterns of biodiversity. Here, we review North American arthropod collections using two key metrics, specimen holdings and digitization efforts, to assess the potential for collections to provide needed biodiversity data. We include data from 223 arthropod collections in North America, with an emphasis on the United States. Our specific findings are as follows: (1) The majority of North American natural history collections (88%) and specimens (89%) are located in the United States. Canada has comparable holdings to the United States relative to its estimated biodiversity. Mexico has made the furthest progress in terms of digitization, but its specimen holdings should be increased to reflect the estimated higher Mexican arthropod diversity. The proportion of North American collections that has been digitized, and the number of digital records available per species, are both much lower for arthropods when compared to chordates and plants. (2) The National Science Foundation's decade-long ADBC program (Advancing Digitization of Biological Collections) has been transformational in promoting arthropod digitization. However, even if this program became permanent, at current rates, by the year 2050 only 38% of the existing arthropod specimens would be digitized, and less than 1% would have associated digital images. (3) The number of specimens in collections has increased by approximately 1% per year over the past 30 years. We propose that this rate of increase is insufficient to provide enough data to address biodiversity research needs, and that arthropod collections should aim to triple their rate of new specimen acquisition. (4) The collections we surveyed in the United States vary broadly in a number of indicators. Collectively, there is depth and breadth, with smaller collections providing regional depth and larger collections providing greater global coverage. (5) Increased coordination across museums is needed for digitization efforts to target taxa for research and conservation goals and address long-term data needs. Two key recommendations emerge: collections should significantly increase both their specimen holdings and their digitization efforts to empower continental and global biodiversity data pipelines, and stimulate downstream research.
| S-EPMC6882419 | biostudies-literature
Project description:The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.
| S-EPMC8010649 | biostudies-literature
Project description:IntroductionCancer is a significant public health challenge globally, with nearly 2000 lives lost daily in Africa alone. Without adequate measures, mortality rates are likely to increase. The major challenge for cancer care in Africa is equity and prioritization, as cancer is not receiving adequate attention from policy-makers and strategic stakeholders in the healthcare space. This neglect is affecting the three primary tiers of cancer care: prevention, diagnosis, and treatment/management. To promote cancer care equity, addressing issues of equity and prioritization is crucial to ensure that everyone has an equal chance at cancer prevention, early detection, and appropriate care and follow-up treatment.MethodologyUsing available literature, we provide an overview of the current state of cancer care in Africa and recommendations to close the gap.ResultsWe highlight several factors that contribute to cancer care inequity in Africa, including inadequate funding for cancer research, poor cancer education or awareness, inadequate screening or diagnostic facilities, lack of a well-organized and effective cancer registry system and access to care, shortage of specialized medical staff, high costs for screening, vaccination, and treatment, lack of technical capacity, poor vaccination response, and/or late presentation of patients for cancer screening. We also provide recommendations to address some of these obstacles to achieving cancer care equity. Our recommendations are divided into national-level initiatives and capacity-based initiatives, including cancer health promotion and awareness by healthcare professionals during every hospital visit, encouraging screening and vaccine uptake, ensuring operational regional and national cancer registries, improving healthcare budgeting for staff, equipment, and facilities, building expertise through specialty training, funding for cancer research, providing insurance coverage for cancer care, and implementing mobile health technology for telemedicine diagnosis.ConclusionAddressing challenges to cancer equity holistically would improve the likelihood of longer survival for cancer patients, lower the risk factors for groups that are already at risk, and ensure equitable access to cancer care on the continent. This study identifies the existing stance that African nations have on equity in cancer care, outlines the current constraints, and provides suggestions that could make the biggest difference in attaining equity in cancer care.
| S-EPMC10496173 | biostudies-literature
Project description:Carcinogenicity refers to a highly toxic end point of certain chemicals, and has become an important issue in the drug development process. In this study, three novel ensemble classification models, namely Ensemble SVM, Ensemble RF, and Ensemble XGBoost, were developed to predict carcinogenicity of chemicals using seven types of molecular fingerprints and three machine learning methods based on a dataset containing 1003 diverse compounds with rat carcinogenicity. Among these three models, Ensemble XGBoost is found to be the best, giving an average accuracy of 70.1?±?2.9%, sensitivity of 67.0?±?5.0%, and specificity of 73.1?±?4.4% in five-fold cross-validation and an accuracy of 70.0%, sensitivity of 65.2%, and specificity of 76.5% in external validation. In comparison with some recent methods, the ensemble models outperform some machine learning-based approaches and yield equal accuracy and higher specificity but lower sensitivity than rule-based expert systems. It is also found that the ensemble models could be further improved if more data were available. As an application, the ensemble models are employed to discover potential carcinogens in the DrugBank database. The results indicate that the proposed models are helpful in predicting the carcinogenicity of chemicals. A web server called CarcinoPred-EL has been built for these models ( http://ccsipb.lnu.edu.cn/toxicity/CarcinoPred-EL/ ).
| S-EPMC5437031 | biostudies-literature
Project description:BackgroundThe purpose of this paper is to describe the Automated Heart-Health Assessment (AH-HA) study protocol, which demonstrates an agile approach to cancer care delivery research. This study aims to assess the effect of a clinical decision support tool for cancer survivors on cardiovascular health (CVH) discussions, referrals, completed visits with primary care providers and cardiologists, and control of modifiable CVH factors and behaviors. The COVID-19 pandemic has caused widespread disruption to clinical trial accrual and operations. Studies conducted with potentially vulnerable populations, including cancer survivors, must shift towards virtual consent, data collection, and study visits to reduce risk for participants and study staff. Studies examining cancer care delivery innovations may also need to accommodate the increased use of virtual visits.Methods/designThis group-randomized, mixed methods study will recruit 600 cancer survivors from 12 National Cancer Institute Community Oncology Research Program (NCORP) practices. Survivors at intervention sites will use the AH-HA tool with their oncology provider; survivors at usual care sites will complete routine survivorship visits. Outcomes will be measured immediately after the study visit, with follow-up at 6 and 12 months. The study was amended during the COVID-19 pandemic to allow for virtual consent, data collection, and intervention options, with the goal of minimizing participant-staff in-person contact and accommodating virtual survivorship visits.ConclusionsChanges to the study protocol and procedures allow important cancer care delivery research to continue safely during the COVID-19 pandemic and give sites and survivors flexibility to conduct study activities in-person or remotely.
| S-EPMC8220316 | biostudies-literature
Project description:ObjectivesOpen-access cancer imaging datasets have become integral for evaluating novel AI approaches in radiology. However, their use in quantitative analysis with radiomics features presents unique challenges, such as incomplete documentation, low visibility, non-uniform data formats, data inhomogeneity, and complex preprocessing. These issues may cause problems with reproducibility and standardization in radiomics studies.MethodsWe systematically reviewed imaging datasets with public copyright licenses, published up to March 2023 across four large online cancer imaging archives. We included only datasets with tomographic images (CT, MRI, or PET), segmentations, and clinical annotations, specifically identifying those suitable for radiomics research. Reproducible preprocessing and feature extraction were performed for each dataset to enable their easy reuse.ResultsWe discovered 29 datasets with corresponding segmentations and labels in the form of health outcomes, tumor pathology, staging, imaging-based scores, genetic markers, or repeated imaging. We compiled a repository encompassing 10,354 patients and 49,515 scans. Of the 29 datasets, 15 were licensed under Creative Commons licenses, allowing both non-commercial and commercial usage and redistribution, while others featured custom or restricted licenses. Studies spanned from the early 1990s to 2021, with the majority concluding after 2013. Seven different formats were used for the imaging data. Preprocessing and feature extraction were successfully performed for each dataset.ConclusionRadiomicsHub is a comprehensive public repository with radiomics features derived from a systematic review of public cancer imaging datasets. By converting all datasets to a standardized format and ensuring reproducible and traceable processing, RadiomicsHub addresses key reproducibility and standardization challenges in radiomics.Critical relevance statementThis study critically addresses the challenges associated with locating, preprocessing, and extracting quantitative features from open-access datasets, to facilitate more robust and reliable evaluations of radiomics models.Key points- Through a systematic review, we identified 29 cancer imaging datasets suitable for radiomics research. - A public repository with collection overview and radiomics features, encompassing 10,354 patients and 49,515 scans, was compiled. - Most datasets can be shared, used, and built upon freely under a Creative Commons license. - All 29 identified datasets have been converted into a common format to enable reproducible radiomics feature extraction.
| S-EPMC10716101 | biostudies-literature
Project description:BACKGROUND:An individual's response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. RESULTS:Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. CONCLUSIONS:Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance of evaluating the impact of exposure across cell-types, as the effect is responsive to the cellular environment. These comparative genetic results support the concept of a cell-gene-environment interaction.
| S-EPMC7247264 | biostudies-literature