Real-time Biology Research Articles

Pre-treatment metastatic biopsy: a step towards precision oncology for urothelial cancer.

Early metastatic spread and clonal expansion of individual mutations result in a heterogeneous tumour landscape in metastatic urothelial cancer (mUC). Substantial molecular heterogeneity of common drug targets, such as membranous NECTIN4, FGFR3 mutations, PDL1 or immune phenotypes, has been documented between primary and metastatic tumours. However, translational and clinical studies frequently do not account for such heterogeneity and often investigate primary tumour samples that might not be representative in patients with mUC. We propose this as a potential factor for why many biomarkers for mUC have failed to be integrated into clinical practice. Fresh pre-treatment metastatic biopsies enable the capturing of prevailing tumour biology in real time. The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody-drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.

Advancements in Molecular Imaging for the Diagnosis and Management of Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) is a growing global health burden with high incidence and mortality rates. Despite advances in surgical techniques and perioperative care, outcomes after surgical treatment have not improved over the past three decades. Molecular imaging is an emerging field that enables researchers to study diseases at the molecular and cellular levels, enabling the detection of elevated serum α-fetoprotein (AFP) and abnormal expressions of various HCC-specific and nonspecific cell surface antigens and intracellular targets. Molecular imaging techniques detect liver lesions at the molecular and cellular level, allowing early detection and accurate staging of HCC. Positron emission tomography (PET) imaging offers greater sensitivity and specificity, while hepatobiliary-specific radiotracers with SPECT imaging provide insights into benign and malignant lesion differentiation. Radiomics and artificial intelligence are vital in deciphering molecular imaging data, with machine learning algorithms boosting diagnostic gains and predicting treatment response. Theranostics, a state-of-the-art application, provides diagnostic and therapeutic leverage following a single imaging agent. By understanding tumor biology in real time, radiopharmaceuticals can be transformed into personalized radiotherapies, enabling clinicians to make science-driven decisions throughout the illness. Future directions include developing novel radiotracers and integrating AI into clinical decision-making. Collaboration between academic researchers, clinicians, and industry colleagues is crucial to converting exciting advances into improved clinical outcomes for HCC patients.

Tissue Proteomic Approaches to Understand the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) has become a global disease encompassing a group of progressive disorders characterized by recurrent chronic inflammation of the gut with variable disease courses and complications. Despite recent advances in the knowledge of IBD pathophysiology, the elucidation of its etiopathology and progression is far from fully understood, requiring complex and multiple approaches. Therefore, limited clinical progress in diagnosis, assessment of disease activity, and optimal therapeutic regimens have been made over the past few decades. This review explores recent advances and challenges in tissue proteomics with an emphasis on biomarker discovery and better understanding of the molecular mechanisms underlying IBD pathogenesis. Future multi-omic studies are required for the comprehensive molecular characterization of disease biology in real time with a future impact on early detection, disease monitoring, and prediction of the clinical outcome.

SMAUG: Analyzing single-molecule tracks with nonparametric Bayesian statistics.

Single-molecule fluorescence microscopy probes nanoscale, subcellular biology in real time. Existing methods for analyzing single-particle tracking data provide dynamical information, but can suffer from supervisory biases and high uncertainties. Here, we develop a method for the case of multiple interconverting species undergoing free diffusion and introduce a new approach to analyzing single-molecule trajectories: the Single-Molecule Analysis by Unsupervised Gibbs sampling (SMAUG) algorithm, which uses nonparametric Bayesian statistics to uncover the whole range of information contained within a single-particle trajectory dataset. Even in complex systems where multiple biological states lead to a number of observed mobility states, SMAUG provides the number of mobility states, the average diffusion coefficient of single molecules in that state, the fraction of single molecules in that state, the localization noise, and the probability of transitioning between two different states. In this paper, we provide the theoretical background for the SMAUG analysis and then we validate the method using realistic simulations of single-particle trajectory datasets as well as experiments on a controlled in vitro system. Finally, we demonstrate SMAUG on real experimental systems in both prokaryotes and eukaryotes to measure the motions of the regulatory protein TcpP in Vibrio cholerae and the dynamics of the B-cell receptor antigen response pathway in lymphocytes. Overall, SMAUG provides a mathematically rigorous approach to measuring the real-time dynamics of molecular interactions in living cells.

Sports Injuries: Diagnosis, Prevention, Stem Cell Therapy, and Medical Sport Strategy.

Sports injuries diagnosis, prevention, and treatment are the most important issues of sports medicine. Fortunately, sports injuries are often treated effectively, and people with damage recover and return to the sport in a satisfactory condition. Meanwhile, many sports injuries and complications can be prevented. In general, sports injuries include acute or chronic injuries. Given increasing in popularity, sports medicine doctors use stem cells to treat a wide variety of sports injuries, including damage to tendons, ligaments, muscles, and cartilage. Stem cell therapy to an injured area could be done through direct surgical application, stem-cell-bearing sutures, and injection. Stem cell therapy holds potential for repair and functional plasticity following sports injuries compared to traditional methods; however, the mechanism of stem cell therapy for sports injuries remains largely unknown. Medical imaging technologies provide the hope to ample the knowledge concerning basic stem cell biology in real time when transplanted into sport-induced damaged organs. Using stem cell treatment might restore continuity and regeneration and promote growth back the organ targets. Besides, using a noninvasive medical imaging method would have the long-time monitoring advantage to the stem cells transplanting individual. The multimodality imaging technique allows for studying acute pathological events following sports injuries; therefore, the use of imaging techniques in medicine permits the straight examination of dynamic regenerative events of specific stem cells following a sports injury in people.

WS8-1 - Current landscape and future perspectives of biomarker study in breast cancer

Breast cancer (BC) is a heterogeneous disease encompassing multiple tumor subtypes with distinct morphology, behavior and clinical implications. Biomarkers play an essential role in the management of women with BC. The appropriate use of molecular biomarkers enables us for patients with BC to receive optimal treatment. Established biomarkers, such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67, play significant roles in BC to predict the prognosis and decide the specific therapy to each patient. According to current guidelines, the additional biopsy from tumor tissues at metastatic sites is recommended for the analysis of current status of the diseases. However, difficulties in obtaining tumor tissues at metastatic sites frequently hinders clinicians to perform biopsies from metastatic tumors, and clinicians often depends on the phenotype of the primary tumor for the treatment decisions in metastatic breast cancer. In addition, serial tissue biopsy sampling is essential for the evaluation of current disease status but, this cannot be easily accomplished, are sometimes inaccessible or may not fully reflect tumor heterogeneity. Recently, liquid biopsy enables us to analyze several circulating biomarkers such as circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) in the blood of patients and could give us useful information on the current disease status. Assessing tumor biology in real time by CTCs or ctDNA may serve to detect minimal residual disease, discover therapeutic targets, and predict response to treatment. In this paper, I will cover the potential role of biomarkers on overcoming tumor heterogeneity, on their potential relevance for tumor surveillance and monitoring, and for the selection of therapeutic options.

Smart Microscopy for Multi-Scale Developmental Biology in Real-Time

Smart Microscopy for Multi-Scale Developmental Biology in Real-Time

Cambridge Healthtech Institute's Third Annual Anti-inflammatories: Small Molecules Meeting, April 17th – 18th 2012, San Diego, USA

The Third Annual Cambridge Healthtech Institute (CHI) sponsored meeting of Anti-inflammatories: Small Molecules was held in San Diego from the 17th to the 18th of April 2012. It comprised of approximately 70 attendees from both large and small pharma and academic institutes from around the world. The meeting drew on the wide ranging application of targeting drugs which have anti-inflammatory activity and which modulate the immune response in a number of human diseases. These included rheumatoid arthritis (RA) and asthma, multiple sclerosis (MS), inflammatory bowel disease (IBD) and multiple myeloma (MM). Data was presented supporting all stages of drug discovery from target identification and validation through to lead identification and optimization and both early and late stage clinical development. A keynote address by Paul Garside (Institute of Infection, Immunology and Inflammation, University of Glasgow) was devoted to investigating components of immune response biology in real time in vivo and the potential of this rapidly developing field to dissect biological mechanism at a cellular level. This report contains selected highlights from the meeting and concludes with some perspectives on the challenges and opportunities facing drug discovery and development.

Components of a Curriculum for Molecular Imaging Scientists

Molecular imaging is the visualization, characterization, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems (1). It comprises an emerging set of technologies that builds on advances in imaging procedures (e.g., PET, SPECT, MRI, ultrasound, optical, and photoacoustic), improved understanding of biology, and the development of molecularly targeted agents. These continuously expanding sets of imaging methods are often used in combination, and advances in data acquisition and analyses facilitate a more complete understanding of biology. Molecular imaging aims to improve our understanding of mammalian biology and lead to advances in patient care by providing targeted therapies that will enable personalized medicine and the imaging tools to assess outcome. Implementation of these new technologies in clinical care has many educational, technical, and regulatory challenges that must be overcome before molecular imaging reaches its full potential. The impact of molecular imaging has been significant in several disciplines, because it represents a paradigm shift in how scientists and clinicians can observe biology in real time and in a relatively noninvasive manner to enable the power of repeated measures in living organisms.

My Dream of a Fantastic Voyage to See the Inner Workings of a Cell

What would I give to be allowed to embark on a Fantastic Voyage at the nanometer scale inside the cell! In the 1960's film, humans were shrunk down to merely micrometer scale, but we now know that “nano” is the ticket. Imagine being able to observe cellular structural biology in real time and to see proteins and nucleic acids in action, in the concentrated environment of the nucleus, let alone in the cytosol. I imagine a complex molecular ballroom full of many intricately choreographed dancers, changing partners, switching locations, dying and being born again. Imagine the purpose and chaos governing the survival of the cellular microcosm, there for me (for you) to see and ultimately understand. Eva Nogales. Photo by Paul Fetters for HHMI. As a structural biologist, initially trained as a physicist, cells often seem too complex and far afield from my own research. My scientific presentations typically borrow images from cell biologists' websites, and I warn my audience after the first introductory slides that no more cells will be seen for the rest of the talk. However, as a molecular electron microscopist working on the cytoskeleton and large macromolecular complexes, I boast in front of crystallographers and nuclear magnetic resonance experts that we study fully functional complexes, in as close to physiological conditions as one can possibly expect outside of a cell. However, this is obviously not as physiological as if we were visualizing the native complexes in their cellular context! With fully annotated genomes providing nearly complete cellular parts lists, and with ever more powerful light microscopy, among other 21st century techniques, we have come a long way toward understanding the inner workings of the cell. Still, the dream of visualizing the intact cell's anatomy with molecular resolution seems like science fiction. Is there any hope for visualizing these molecular machines where they function and when it matters, even if it is not through our atomically shrunk, craving eyes? I really want to think so. It may not come from a single instrument, like the Star Trek scope where magnification can be cranked until the bar code on individual atoms becomes clear. However, combining currently available methodologies and then taking them to the next level may, step by step, get us there. The first combined electron and light microscopes are already producing data wherein the fluorescent colors of choice are superimposed on the gray levels of individual molecular density. Spectroscopy readings, with nanometer cube mapping capability, are being carved out of cellular slices in futuristic attempts at spatial metabolomics. Three-dimensional maps of hydrated cells will soon become routine, and as the resolution moves from 100 to 10 Å in my life time (if I take good care of myself), we will be able to identify macromolecules by shapes, in snapshots of cellular life. We will be able to follow the paths of single proteins as they meander their way along the chaotic cellular freeways of the cytoskeleton, or fluidly traffic between cellular compartments. We are almost there. My own personal dream of “visualizing” the complete kinetochore protein network, carrying out the dynamic engagement of chromosomes to the mitotic spindle and thus revealing the force coupling mechanism, may be just around the corner. It is not that images are worth a thousand gels, or movies a million pulldowns (although perhaps they are), it's just my own preferred means of getting to know and understand nature. My wish for the future of cell biology: I want to “see” the cell (I leave smelling it and listening to it to biochemists and theoretical physicists, respectively).