Is translational research compatible with preclinical publication strategies?
The term "translational research" is used to describe the transfer of basic biological knowledge into practical medicine, a process necessary for motivation of public spending. In the area of cancer therapeutics, it is becoming increasingly evident that results obtained in vitro and in animal models are difficult to translate into clinical medicine. We here argue that a number of factors contribute to making the translation process inefficient. These factors include the use of sensitive cell lines and fast growing experimental tumors as targets for novel therapies, and the use of unrealistic drug concentrations and radiation doses. We also argue that aggressive interpretation of data, successful in hypothesis-building biological research, does not form a solid base for development of clinically useful treatment modalities. We question whether "clean" results obtained in simplified models, expected for publication in high-impact journals, represent solid foundations for improved treatment of patients. Open-access journals such as Radiation Oncology have a large mission to fulfill by publishing relevant data to be used for making actual progress in translational cancer research. (+info)
Telomerase immunity from bench to bedside: round one.
Telomerase, a reverse transcriptase primarily devoted to the elongation of telomeres in mammalian cells, is also the first bona fide common tumor antigen. In fact, telomerase is over-expressed in > 85% of tumor cells irrespective of origin and histological type. In the past seven years, there has been considerable interest in assessing telomerase as substrate for vaccination in cancer patients to induce CD8 T cell responses. Because the activation of T cells is restricted by the MHC molecules on antigen presenting cells or tumor cells, the identification of telomerase peptides immunogenic for humans is tightly linked with HLA types. To date, a handful of peptides have been identified through a variety of screening procedures, including bioinformatics prediction, in vivo immunization of HLA transgenic mice, in vitro immunization of PBMC from normal donors and cancer patients, and processing in human tumor cells. Currently, there exist putative peptides for five major HLA types (A2, A1, A3, A24 and B7). Due to the complexity of the HLA system, trials have been performed focusing on the most prevalent HLA type, HLA-A2. Here, we summarize this collective effort and highlight results obtained in Phase 1 trials including a Phase 1 trial performed at the UCSD Cancer Center. (+info)
In support of descriptive studies; relevance to translational research.
The contemporary scientific establishment equates hypothesis testing to good science. This stance bypasses the preliminary need to identify a worthwhile hypothesis through rigorous observation of natural processes. If alleviation of human suffering is claimed as the goal of a scientific undertaking, it would be unfair to test a hypothesis whose relevance to human disease has not been satisfactorily proven. Here, we argue that descriptive investigations based on direct human observation should be highly valued and regarded essential for the selection of worthwhile hypotheses while the pursuit of costly scientific investigations without such evidence is a desecration of the cause upon which biomedical research is grounded. (+info)
Supporting the design of translational clinical studies through the generation and verification of conceptual knowledge-anchored hypotheses.
The ability to generate hypotheses based upon the contents of large-scale, heterogeneous data sets is critical to the design of translational clinical studies. In previous reports, we have described the application of a conceptual knowledge engineering technique, known as constructive induction (CI) in order to satisfy such needs. However, one of the major limitations of this method is the need to engage multiple subject matter experts to verify potential hypotheses generated using CI. In this manuscript, we describe an alternative verification technique that leverages published biomedical literature abstracts. Our report will be framed in the context of an ongoing project to generate hypotheses related to the contents of a translational research data repository maintained by the CLL Research Consortium. Such hypotheses will are intended to inform the design of prospective clinical studies that can elucidate the relationships that may exist between biomarkers and patient phenotypes. (+info)
Discovering synergistic qualities of published authors to enhance translational research.
Translational research is the process of bringing together basic scientific research and improvements in patient care. This process, by its very nature, requires a wide range of skills and resources, typically not found within any single individual. This project investigates the synergistic features of published researchers at the Oregon Clinical and Translational Research Institute(OCTRI) to see how scientists with different specializations can be brought together to improve translational research.The investigated features were author connectivity and complementarity of research subjects. Author connectivity was measured by taking the Average Path Length (APL) and cluster coefficients  over an OCTRIcoauthor network. A high degree of connectivity, or low APL value, would indicate that a researcher has participated in many collaborations and published many papers with other OCTRI researchers. This would imply that they have some experience we could leverage to build teams for translational research. Subject complementarity was established by using pairs of frequently co-occurring MeSH terms. Those terms were then used to bridge researchers together through indirect Swanson matching  and present evidence of topic synergy, or potential collaborative synergy.Our initial investigation supports the development of a collaborative browsing tool to assist the creation of new translational research teams. Such a tool is being developed at the OCTRI and will include a user-centric evaluation in the near future. (+info)
Translational research into gut microbiota: new horizons in obesity treatment.
Lost in translation: what is limiting cardiomyoplasty and can tissue engineering help?
Heart failure accounts for more deaths in the United States than any other detrimental human pathology. Recently, repairing the heart after seemingly irreversible injury leading to heart failure appears to have come within reach. Cellular cardiomyoplasty, transplanting viable cell alternatives into the diseased myocardium, has emerged as a promising possible solution. Translating this approach from the laboratory to the clinic, however, has been met with several challenges, leaving many questions unanswered. This review assesses the state of investigation of several progenitor cell sources, including induced pluripotent stem cells, embryonic stem cells, bone marrow stem cells, adipose-derived adult stem cells, amniotic fluid stem cells, skeletal muscle progenitors, induced pluripotent stem cells and cardiac progenitors. Several current roadblocks to maximum success are discussed. These include understanding the need for cardiomyocyte differentiation, appreciating the role of paracrine factors, and addressing the low engraftment rates using current techniques. Tissue engineering strategies to address these obstacles and to help maximize cellular cardiomyoplasty success are reviewed. (+info)
Blast-related brain injury: imaging for clinical and research applications: report of the 2008 st. Louis workshop.