TAILORx: Questions Answered, Lessons Learned, and Remaining Knowledge Gaps.
Ontology highlight
ABSTRACT:
SUBMITTER: Sparano JA
PROVIDER: S-EPMC6881095 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
TAILORx: Questions Answered, Lessons Learned, and Remaining Knowledge Gaps.
Sparano Joseph A JA Gray Robert R
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20190607 21
Similar Datasets
Project description:Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.
| S-EPMC7795616 | biostudies-literature
Project description:Northern wetlands play a key role in the global carbon budget, particularly in the budgets of the greenhouse gas methane. These ecosystems also determine the hydrology of northern rivers and represent one of the largest reservoirs of fresh water in the Northern Hemisphere. Sphagnum-dominated peat bogs and fens are the most extensive types of northern wetlands. In comparison to many other terrestrial ecosystems, the bacterial diversity in Sphagnum-dominated wetlands remains largely unexplored. As demonstrated by cultivation-independent studies, a large proportion of the indigenous microbial communities in these acidic, cold, nutrient-poor, and water-saturated environments is composed of as-yet-uncultivated bacteria with unknown physiologies. Most of them are slow-growing, oligotrophic microorganisms that are difficult to isolate and to manipulate in the laboratory. Yet, significant breakthroughs in cultivation of these elusive organisms have been made during the last decade. This article describes the major prerequisites for successful cultivation of peat-inhabiting microbes, gives an overview of the currently captured bacterial diversity from northern wetlands and discusses the unique characteristics of the newly discovered organisms.
| S-EPMC3174395 | biostudies-literature
Project description:Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.
| S-EPMC4731128 | biostudies-literature
Project description:IntroductionDuring the past 2 decades, basic research deciphering the underlying mechanisms of nociception and chronic pain was thought to finally step beyond opioids and nonsteroidals and provide patients with new analgesics. But apart from calcitonin gene-related peptide antagonists, nothing arrived in hands of clinicians.ObjectivesTo present existing evidence of 3 representative target molecules in the development of novel pain treatment that, so far, did not result in approved drugs.MethodsThis Clinical Update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews best available evidence and practice.ResultsWe highlight 3 targets: a ion channel, a neuronal growth factor, and a neuropeptide to explore why these drug targets have been dropped in clinical phase II-III trials. Antibodies to nerve growth factor had very good effects in musculoskeletal pain but resulted into more patients requiring joint replacements. Blockers of NaV1.7 were often not effective enough-at least if patients were not stratified. Blockers of neurokinin receptor were similarly not successful enough. In general, failure was most often to the result of a lack of effect and to a lesser extend because of unexpected severe side effects. However, all studies and trials lead to an enormous move in the scientific community to better preclinical models and testing as well as revised methods to molecularly phenotype and stratify patients.ConclusionAll stakeholders in the process can help in the future: better preclinical studies, phenotyping and stratifying patients, and participation in clinical trials to move the discovery of analgesics forward.
| S-EPMC10624476 | biostudies-literature
Project description:Evidence supporting the use of balloon pulmonary angioplasty #BPA, which has drastically changed management of non-operable chronic thromboembolic pulmonary hypertension #CTEPH, and rationale for a future multimodal approach with combined medical therapy https://bit.ly/3F7ccKD.
| S-EPMC9973525 | biostudies-literature
Project description:This review compiles the current state of controversial aspects of liver failure and outlines future challenges. The definition of acute liver failure (ALF) is widely accepted and implies no previous liver injury whereas the term "acute-on-chronic liver failure" remains contested. We will promote a concept, in which we differentiate three types of liver failure: ALF, acute-on-chronic liver failure (AOCLF) and acute-on-liver-cirrhosis (AOCi). The mechanistical insights into the coagulation system in patients with hepatic insufficiency have increased fundamentally in the past 10 years. Therefore, we follow now the concept of the so-called rebalanced hemostasis. This lower-level equilibrium arises from the fact that most coagulation factors and inhibitors are synthesized within the liver. We will demonstrate the advantage of viscoelastic test methods, which can assess the coagulation situation in patients with liver insufficiency much more precisely than conventional global coagulation tests. The therapeutic option of emergency liver transplantation (ELT) has significantly improved the prognosis of patients with ALF. However, limiting factors such as shortage of organs increase more and more the need for reliable prognostic markers. Due to a better understanding of the regenerative process during ALF new survival markers and prognostic tools have been emerging on the horizon in the last decade. Therefore, we will describe the current state of research in this field.
| S-EPMC8106069 | biostudies-literature
Project description:BackgroundEnhancing interoperability of bioinformatics knowledge bases is a high-priority requirement to maximize data reusability and thus increase their utility such as the return on investment for biomedical research. A knowledge base may provide useful information for life scientists and other knowledge bases, but it only acquires exchange value once the knowledge base is (re)used, and without interoperability, the utility lies dormant.ResultsIn this article, we discuss several approaches to boost interoperability depending on the interoperable parts. The findings are driven by several real-world scenario examples that were mostly implemented by Bgee, a well-established gene expression knowledge base. To better justify the findings are transferable, for each Bgee interoperability experience, we also highlight similar implementations by major bioinformatics knowledge bases. Moreover, we discuss ten general main lessons learned. These lessons can be applied in the context of any bioinformatics knowledge base to foster data reusability.ConclusionsThis work provides pragmatic methods and transferable skills to promote reusability of bioinformatics knowledge bases by focusing on interoperability.
| S-EPMC10433096 | biostudies-literature
Project description:Brain diseases are a major cause of death and disability worldwide and contribute significantly to years of potential life lost. Although there have been considerable advances in biological mechanisms associated with brain disorders as well as drug discovery paradigms in recent years, these have not been sufficiently translated into effective treatments. This Special Article expands on Keystone Symposia's pre- and post-pandemic panel discussions on translational neuroscience research. In the article, we discuss how lessons learned from the COVID-19 pandemic can catalyze critical progress in translational research, with efficient collaboration bridging the gap between basic discovery and clinical application. To achieve this, we must place patients at the center of the research paradigm. Furthermore, we need commitment from all collaborators to jointly mitigate the risk associated with the research process. This will require support from investors, the public sector and pharmaceutical companies to translate disease mechanisms into world-class drugs. We also discuss the role of scientific publishing in supporting these models of open innovation. Open science journals can now function as hubs to accelerate progress from discovery to treatments, in neuroscience in particular, making this process less tortuous by bringing scientists together and enabling them to exchange data, tools and knowledge effectively. As stakeholders from a broad range of scientific professions, we feel an urgency to advance brain disease therapies and encourage readers to work together in tackling this challenge.
| S-EPMC9844134 | biostudies-literature
Project description:BackgroundEffective knowledge transfer of eLearning objects can hasten the adoption and dissemination of technology in teaching and learning. However, challenges exist which hinder inter-organisational knowledge transfer, particularly across continents. The ACoRD project aimed to transfer knowledge on digital learning development from UK/EU (provider) to Malaysian (receiver) higher education institutions (HEIs). This study explores the challenges encountered during the knowledge transfer process and lessons learned.MethodsThis is a qualitative study involving both the knowledge providers and receivers in focus group discussions (n = 25). Four focus group discussions were conducted in the early (n = 2) and mid-phase (n = 2) of the project by trained qualitative researchers using a topic guide designed to explore experiences and activities representing knowledge transfer in multi-institutional and multi-cultural settings. The interviews were audio-recorded, transcribed verbatim, and checked. The transcripts were analysed using thematic analysis.ResultsFive main themes emerged from this qualitative study: mismatched expectations between providers and receivers; acquiring new knowledge beyond the professional "comfort zone"; challenges in cascading newly acquired knowledge to colleagues and management; individual and organisational cultural differences; and disruption of knowledge transfer during the COVID-19 pandemic.ConclusionThis study highlights the need to create a conducive platform to facilitate continuous, timely and bi-directional needs assessment and feedback; this should be done in the early phase of the knowledge transfer process. The challenges and strategies identified in this study could guide more effective knowledge transfer between organisations and countries.
| S-EPMC9488788 | biostudies-literature
Project description:Wildfires have increased in frequency and area burned, trends expected to continue with climate change. Among other effects, fires release pollutants into the atmosphere, representing a risk to human health and downwind terrestrial and aquatic ecosystems. While human health risks are well studied, the ecological impacts to downwind ecosystems are not, and this gap may present a constraint on developing an adequate assessment of the ecological risks associated with downwind wildfire exposure. Here, we first screened the scientific literature to assess general knowledge about pathways and end points of a conceptual model linking wildfire generated pollutants and other materials to downwind ecosystems. We found a substantial body of literature on the composition of wildfire derived pollution and materials in the atmosphere and subsequent transport, yet little observational or experimental work on their effects on downwind ecological end points. This dearth of information raises many questions related to adequately assessing the ecological risk of downwind exposure, especially given increasing wildfire trends. To guide future research, we pose eight questions within the well-established US EPA ecological risk assessment paradigm that if answered would greatly improve ecological risk assessment and, ultimately, management strategies needed to reduce potential wildfire impacts.
| S-EPMC11345788 | biostudies-literature