Activity

Intravital microscopy (IVM) and optical coherency tomography (OCT) are two powerful optical imaging tools that allow visualization of dynamic biological activities in living subjects with subcellular resolutions. Recent advances in labeling and label-free techniques empower IVM and OCT for a wide range of preclinical and clinical cancer imaging, providing profound insights into the complex physiological, cellular, and molecular behaviors of tumors. Preclinical IVM and OCT have elucidated many otherwise inscrutable aspects of cancer biology, while clinical applications of IVM and OCT are revolutionizing cancer diagnosis and therapies. We review important progress in the fields of IVM and OCT for cancer imaging in living subjects, highlighting key technological developments and their emerging applications in fundamental cancer biology research and clinical oncology investigation. The collection of microbes that live in and on the human body – the human microbiome – can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology – a systems biology approach. Saracatinib Immunotherapy (IO) has altered the therapeutic landscape for multiple cancers. There are emerging data from retrospective studies on a subset of patients who do not benefit from IO, instead experiencing rapid progression with dramatic acceleration of disease trajectory, termed ‘hyperprogressive disease’ (HPD). The incidence of HPD ranges from 4% to 29% from the studies reported. Biological basis and mechanisms of HPD are currently being elucidated, with one theory involving the Fc region of antibodies. Another group has shown EGFR and MDM2/MDM4 amplifications in patients with HPD. This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease. Thus, prospective studies are urgently needed to confirm the underlying biology, predict patients who are susceptible to HPD, and determine the modality of therapy post progression. Mounting evidence links genetic lesions with genome topology alterations and aberrant gene activation. However, the role of epigenetic plasticity remains elusive. Emerging studies implicate DNA methylation, transcriptional elongation, long noncoding RNAs (lncRNAs), and CCCTC-binding factor (CTCF)-RNA interactions, but systematic approaches are needed to fully decipher the role of epigenetic plasticity in genome integrity and function. Although immunotherapy has proved to be effective in a variety of cancer subtypes, the role of immune checkpoint inhibition in the treatment of prostate cancer remains unclear. Here we review results from the latest clinical trials and discuss data suggesting that certain genetic mutations may confer increased sensitivity to immune checkpoint blockade. Recent investigations (Rodriguez-Ruiz et al.) have established the counterintuitive idea that delaying apoptosis upon tumor irradiation by caspase 3 inhibition in tumor cells raises the immunogenicity of dying malignant cells. Spatially discordant alternans (SDA) of action potential duration (APD) has been widely observed in cardiac tissue and is linked to cardiac arrhythmogenesis. Theoretical studies have shown that conduction velocity restitution (CVR) is required for the formation of SDA. However, this theory is not completely supported by experiments, indicating that other mechanisms may exist. In this study, we carried out computer simulations using mathematical models of action potentials to investigate the mechanisms of SDA in cardiac tissue. We show that when CVR is present and engaged, such as fast pacing from one side of the tissue, the spatial pattern of APD in the tissue undergoes either spatially concordant alternans or SDA, independent of initial conditions or tissue heterogeneities. When CVR is not engaged, such as simultaneous pacing of the whole tissue or under normal/slow heart rates, the spatial pattern of APD in the tissue can have multiple solutions, including spatially concordant alternans and different SDA patterns, depending on heterogeneous initial conditions or pre-existing repolarization heterogeneities. In homogeneous tissue, curved nodal lines are not stable, which either evolve into straight lines or disappear. However, in heterogeneous itssue, curved nodal lines can be stable, depending on their initial locations and shapes relative to the structure of the heterogeneity. Therefore, CVR-induced SDA and non-CVR-induced SDA exhibit different dynamical properties, which may be responsible for the different SDA properties observed in experimental studies and arrhythmogenesis in different clinical settings. During the preparation of single-stranded DNA catenanes, topological isomers of different linking numbers (Lk) are intrinsically produced, and they must be separated from each other to construct sophisticated nanostructures accurately. In many previous studies, however, mixtures of these isomers were directly employed to construct nanostructures without sufficient characterization. Here, we present a method that easily and clearly characterizes the isomers by polyacrylamide gel electrophoresis. To the mixtures of topological isomers of [2]catenanes, two-strut oligonucleotides, which are complementary with a part of both rings, were added to connect the rings and fix the whole conformations of isomers. As a result, the order of migration rate was always Lk3 > Lk2 > Lk1, irrespective of gel concentration. Thus, all the topological isomers were unanimously characterized by only one polyacrylamide gel electrophoresis experiment. Well-characterized DNA catenanes are obtainable by this two-strut strategy, opening the way to more advanced nanotechnology.