Molecular imaging: interaction between basic and clinical science

One of the major proceedings in the field of gastrointestinal endoscopy has been the advent of molecular imaging, which possesses the potential to have a significant effect on the existing diagnostic and therapeutic paradigms. Molecular imaging encompasses different methods that enable the visualization of disease-specific morphologic or functional alterations of the mucosa based on the molecular signature of individual cells. This development has been made possible by advancements in basic science coupled with technological innovations in endoscopy, both facilitating the identification and characterization of mucosal lesions in vivo based on the lesions' molecular composition rather than their morphologic structure alone. Novel studies based on fluorescent antibody imaging pave the road toward clinical translation and give hope for improved diagnosis and targeted therapies in gastrointestinal diseases.     

Cancer in the elderly: basic science and clinical aspects

The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy.     

A new paradigm for musculoskeletal clinical trials in the UK: the Arthritis Research Campaign (ARC) Clinical Studies Groups initiative

In October 2007, the UK Arthritis Research Campaign (ARC) launched a new approach for the support of clinical trials and related research in the UK. The initiative depends on a partnership between ARC, the UK Clinical Research Network (UKCRN) and the pharmaceutical and related industry. The aim is to develop nationally agreed strategic plans for intervention research for the major musculoskeletal disorders. These will range from testing experimental therapies to novel approaches/ways of using existing interventions, taking advantage of the opportunities afforded for the enhanced support for clinical trials promised by the establishment of local research networks within the National Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN). The initiative encourages greater collaboration with industry with a move to enhance industrial support for research strategies prioritized by the key stakeholders of health care professionals and patients.     

S100A1 in cardiovascular health and disease: Closing the gap between basic science and clinical therapy

Calcium (Ca²⁺) signaling plays a major role in a wide range of physiological functions including control and regulation of cardiac and skeletal muscle performance and vascular tone [1] and [2]. As all Ca²⁺ signals require proteins to relay intracellular Ca²⁺ oscillations downstream to different signaling networks, a specific toolkit of Ca²⁺-sensor proteins involving members of the EF-hand S100 Ca²⁺ binding protein superfamily maintains the integrity of the Ca²⁺ signaling in a variety of cardiac and vascular cells, transmitting the message with great precision and in a temporally and spatially coordinated manner [3], [4], [5] and [6]. Indeed, the possibility that S100 proteins might contribute to heart and vascular diseases was first suggested by the discovery of distinctive patterns of S100 expression in healthy and diseased hearts and vasculature from humans and animal heart failure (HF) models [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17] and [18]. Based on more elaborate genetic studies in mice and strategies to manipulate S100 protein expression in human cardiac, skeletal muscle and vascular cells, it is now apparent that the integrity of distinct S100 protein isoforms in striated muscle and vascular cells such as S100A1, S100A4, S100A6, S100A8/A9 or S100B is a basic requirement for normal cardiovascular and muscular development and function; loss of integrity would naturally lead to profound deregulation of the implicated Ca²⁺ signaling systems with detrimental consequences to cardiac, skeletal muscle, and vascular function [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19] and [20]. The brief debate and discussion here are confined by design to the biological actions and pathophysiological relevance of the EF-hand Ca²⁺-sensor protein S100A1 in the heart, vasculature and skeletal muscle with a particular focus on current translational therapeutic strategies [4], [21] and [23]. By virtue of its ability to modulate the activity of numerous key effector proteins that are essentially involved in the control of Ca²⁺ and NO homeostasis in cardiac, skeletal muscle and vascular cells, S100A1 has been proven to play a critical role both in cardiac performance, blood pressure regulation and skeletal muscle function [4,21,23]. Given that deregulated S100A1 expression in cardiomyocytes and endothelial cells has recently been linked to heart failure and hypertension [4,21,23], it is arguably a molecular target of considerable clinical interest as S100A1 targeted therapies have already been successfully investigated in preclinical translational studies.     

Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (alliance) clinical trials

Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease‐free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non‐APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI ≥30 kg/m². Multivariate Cox proportional‐hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non‐APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03–2.27; P = 0.04) and OS (HR 1.72, 95% CI 1.15–2.58; P = 0.01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non‐APL AML patients. In conclusion, our study indicates that obesity has significant prognostic value for DFS and OS in APL patients, but not for non‐APL AML patients. Am. J. Hematol. 91:199–204, 2016. © 2015 Wiley Periodicals, Inc.     

The relationship between erectile dysfunction and lower urinary tract symptoms: Epidemiological, clinical, and basic science evidence

Lower urinary tract symptoms (LUTS) and sexual dysfunction are highly prevalent in aging men. Both conditions also are significant contributors to overall quality of life. New data have emerged to indicate potential links in epidemiological, physiologic, pathophysiologic, and treatment aspects of these two entities. There are numerous publications based on sophisticated community and clinical-based data, suggesting a strong and consistent association between LUTS and erectile dysfunction (ED). The association is supported by the consistent linear relationship of more severe LUTS with more severe ED. The link between ED and LUTS has biologic plausibility given the four leading theories of how these diseases inter-relate.     

转化医学:基础研究与临床应用间的纽带

转化医学(translational medicine)是欧美生物医学界于上世纪末提出的一个新概念,其目的主要是促进基础研究成果向临床应用的转化。后来其概念进一步演变,内涵和外延不断加深和拓展,目前转化医学通常泛指以解决疾病预防、诊断和治疗等实际问题为导向的医学科研活动,既包括从基础研究成果转化为临床应用的科研活动,也包括从临床问题出发凝练出科学问题、在实验室研究出解决问题的方法再应用于临床的过程。