Overcoming barriers to progress in exercise genomics.
Ontology highlight
ABSTRACT:
SUBMITTER: Bouchard C
PROVIDER: S-EPMC3183378 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
Publications
Overcoming barriers to progress in exercise genomics.
Exercise and sport sciences reviews 20111001 4
This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. ...[more]
Similar Datasets
Project description:DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.
| S-EPMC3273818 | biostudies-other
Project description:More than 13,000 children annually in the United States and Canada under the age of 20 will be diagnosed with cancer at a mortality approaching 20% 1,2. Tumor samples obtained by autopsy provide an innovative way to study tumor progression, potentially aiding in the discovery of new treatments and increased survival rates. The purpose of this study was to identify barriers to autopsies and develop guidelines for requesting autopsies for research purposes.Families of children treated for childhood cancer were referred by patient advocacy groups and surveyed about attitudes and experiences with research autopsies. From 60 interviews, barriers to autopsy and tumor banking were identified. An additional 14 interviews were conducted with medical and scientific experts.Ninety-three percent of parents of deceased children did or would have consented to a research autopsy if presented with the option; however, only half of these families were given the opportunity to donate autopsy tissue for research. The most significant barriers were the physicians' reluctance to ask a grieving family and lack of awareness about research opportunities.The value of donating tumor samples to research via an autopsy should be promoted to all groups managing pediatric cancer patients. Not only does autopsy tumor banking offer a potentially important medical and scientific impact, but the opportunity to contribute this Legacy Gift of autopsy tumor tissue also creates a positive outlet for the grieving family. Taking these findings into account, our multidisciplinary team has developed a curriculum addressing key barriers.
| S-EPMC3522778 | biostudies-literature
Project description:AIM:This paper seeks to describe best practices for conducting cross-language research with individuals who have a language barrier. DESIGN:Discussion paper. DATA SOURCES:Research methods papers addressing cross-language research issues published between 2000-2017. IMPLICATIONS FOR NURSING:Rigorous cross-language research involves the appropriate use of interpreters during the research process, systematic planning for how to address the language barrier between participant and researcher and the use of reliably and validly translated survey instruments (when applicable). Biases rooted in those who enter data into "big data" systems may influence data quality and analytic approaches in large observational studies focused on linking patient language preference to health outcomes. CONCLUSION:Cross-language research methods can help ensure that those individuals with language barriers have their voices contributing to the evidence informing healthcare practice and policies that shape health services implementation and financing. Understanding the inherent conscious and unconscious biases of those conducting research with this population and how this may emerge in research studies is also an important part of producing rigorous, reliable, and valid cross-language research. IMPACT:This study synthesized methodological recommendations for cross-language research studies with the goal to improve the quality of future research and expand the evidence-base for clinical practice. Clear methodological recommendations were generated that can improve research rigor and quality of cross-language qualitative and quantitative studies. The recommendations generated here have the potential to have an impact on the health and well-being of migrants around the world.
| S-EPMC6778489 | biostudies-literature
Project description:HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection.
| S-EPMC5239985 | biostudies-literature
Project description:Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that could be benefited by this state-of-the-art therapeutic modality. Among various causes of the resistance, we here focus on physical stromal barriers that impede the access of immunotherapeutic drug molecules and/or native and engineered immune cells to cancer tissues and cells. Two primary stromal barriers that contribute to the resistance include aberrant tumor vasculatures and excessive extracellular matrix build-ups that restrict extravasation and infiltration, respectively, of molecular and cellular immunotherapeutic agents into tumor tissues. Here, we review the features of these barriers that limit the efficacy of immunotherapy and discuss recent advances that could potentially help immunotherapy overcome the barriers and improve therapeutic outcomes.
| S-EPMC8571040 | biostudies-literature
Project description:Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy. Finally, we address a variety of targeted therapies as a strategy to further amplify immune responses in PAC.
| S-EPMC5848027 | biostudies-literature
Project description:Glioblastoma (GBM) is a highly aggressive and lethal form of primary brain cancer. Numerous barriers exist to the effective treatment of GBM including the tightly controlled interface between the bloodstream and central nervous system termed the 'neurovascular unit,' a narrow and tortuous tumor extracellular space containing a dense meshwork of proteins and glycosaminoglycans, and genomic heterogeneity and instability. A major goal of GBM therapy is achieving sustained drug delivery to glioma cells while minimizing toxicity to adjacent neurons and glia. Targeted nanotherapeutics have emerged as promising drug delivery systems with the potential to improve pharmacokinetic profiles and therapeutic efficacy. Some of the key cell surface molecules that have been identified as GBM targets include the transferrin receptor, low-density lipoprotein receptor-related protein, ?v ?3 integrin, glucose transporter(s), glial fibrillary acidic protein, connexin 43, epidermal growth factor receptor (EGFR), EGFR variant III, interleukin-13 receptor ? chain variant 2, and fibroblast growth factor-inducible factor 14. However, most targeted therapeutic formulations have yet to demonstrate improved efficacy related to disease progression or survival. Potential limitations to current targeted nanotherapeutics include: (1) adhesive interactions with nontarget structures, (2) low density or prevalence of the target, (3) lack of target specificity, and (4) genetic instability resulting in alterations of either the target itself or its expression level in response to treatment. In this review, we address these potential limitations in the context of the key GBM targets with the goal of advancing the understanding and development of targeted nanotherapeutics for GBM. WIREs Nanomed Nanobiotechnol 2017, 9:e1439. doi: 10.1002/wnan.1439 For further resources related to this article, please visit the WIREs website.
| S-EPMC5418115 | biostudies-literature
Project description:Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance.
| S-EPMC4542411 | biostudies-literature
Project description:Aims/questionsTo explore the barriers and facilitators to nurses accessing clinical supervision; explore the barriers and facilitators to organizations implementing clinical supervision and capture what skills nurses require to facilitate clinical supervision.DesignScoping review of peer-reviewed research and grey literature.Data sourcesCINAHL, Medline, PsychINFO and Scopus were searched for relevant papers published between 1990 and 2020. Google, Google Scholar, OpenGrey & EThOS were used to search for grey literature.Review methodsPRISMA-ScR guidelines were used during the literature review process. Eighty-seven papers were included, and data were extracted from each paper using a standardized form. Data synthesis was undertaken using Seidel's analytical framework.ResultsFive themes were identified: Definitions and Models, (Mis) Trust and the Language of Supervision, Alternative Parallel Forums and Support Mechanisms, Time and Cost and Skills required.ConclusionSince its inception in the 1990s, clinical supervision has long been regarded as a supportive platform for nurses to reflect on and develop their practice. However, this review highlights that despite an awareness of the skills required for nurses to undertake clinical supervision, and the facilitators for nurses to access and organizations to implement clinical supervision, there have been persistent barriers to implementation. This review identifies these persistent factors as 'barriers to overcoming the barriers' in the clinical supervision landscape. These require critical consideration to contribute towards moving clinical supervision forward in the spirit of its original intentions.ImpactThis review progresses the debate on clinical supervision through critically analysing the barriers to overcoming the barriers. To this end, the review is designed to stimulate critical discussions amongst nurses in different clinical spaces and key stakeholders such as policy makers and regulatory bodies for the nursing profession.
| S-EPMC9546137 | biostudies-literature
Project description:After a decade of intense preclinical investigations, the first in-class autotaxin inhibitor, GLPG1690, has entered Phase III clinical trials for idiopathic pulmonary fibrosis. In the intervening time, a deeper understanding of the role of the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis in breast cancer progression and treatment resistance has emerged. Concordantly, appreciation of the tumor microenvironment and chronic inflammation in cancer biology has matured. The role of LPA as a central mediator behind these concepts has been exemplified within the breast cancer field. In this review, we will summarize current challenges in breast cancer therapy and delineate how blocking LPA signaling could provide novel adjuvant therapeutic options for overcoming therapy resistance and adverse side effects, including radiation-induced fibrosis. The advent of autotaxin inhibitors in clinical practice could herald their applications as adjuvant therapies to improve the therapeutic indexes of existing treatments for breast and other cancers.
| S-EPMC7072337 | biostudies-literature