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Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Liver metastases often progress from primary cancers including uveal melanoma (UM), breast, and colon cancer. Molecular biomarker imaging is a new non-invasive approach for detecting early stage tumors. Here, we report the elevated expression of chemokine receptor 4 (CXCR4) in liver metastases in UM patients and metastatic UM mouse models, and development of a CXCR4-targeted MRI contrast agent, ProCA32.CXCR4, for sensitive MRI detection of UM liver metastases. ProCA32.CXCR4 exhibits high relaxivities (r 1 = 30.9 mM-1 s-1, r 2 = 43.2 mM-1 s-1, 1.5 T; r 1 = 23.5 mM-1 s-1, r 2 = 98.6 mM-1 s-1, 7.0 T), strong CXCR4 binding (K d = 1.10 ± 0.18 μM), CXCR4 molecular imaging capability in metastatic and intrahepatic xenotransplantation UM mouse models. ProCA32.CXCR4 enables detecting UM liver metastases as small as 0.1 mm3. Further development of the CXCR4-targeted imaging agent should have strong translation potential for early detection, surveillance, and treatment stratification of liver metastases patients. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Secondary drug resistance stems from dynamic clonal evolution during the development of a prior primary resistance. This collateral type of resistance is often a characteristic of cancer recurrence. Yet, mechanisms that drive this collateral resistance and their drug-specific trajectories are still poorly understood. Using resistance selection and small-scale pharmacological screens, we find that cancer cells with primary acquired resistance to the microtubule-stabilizing drug paclitaxel often develop tolerance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), leading to formation of more stable resistant cell populations. We show that paclitaxel-resistant cancer cells follow distinct selection paths under EGFR-TKIs by enriching the stemness program, developing a highly glycolytic adaptive stress response, and rewiring an apoptosis control pathway. Collectively, our work demonstrates the alterations in cellular state stemming from paclitaxel failure that result in collateral resistance to EGFR-TKIs and points to new exploitable vulnerabilities during resistance evolution in the second-line treatment setting. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http//journals.sagepub.com/doi/10.1177/2374289517715040.1. © The Author(s) 2020.The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http//journals.sagepub.com/doi/10.1177/2374289517715040.1. © The Author(s) 2020.The pathologist workforce in the United States is a topic of interest to the health-care community as a whole and to institutions responsible for the training of new pathologists in particular. Although a pathologist shortage has been projected, there has been a pervasive belief by medical students and their advisors that there are "no jobs in pathology." In 2013 and again in 2017, the Program Directors Section of the Association of Pathology Chairs conducted surveys asking pathology residency directors to report the employment status of each of their residents graduating in the previous 5 years. The 2013 Program Directors Section survey indicated that 92% of those graduating in 2010 had obtained employment within 3 years, and 94% of residents graduating in 2008 obtained employment within 5 years. The 2017 survey indicated that 96% of those graduating in 2014 had obtained employment in 3 years, and 97% of residents graduating in 2012 obtained positions within 5 years. These findings are consistent with residents doing 1 or 2 years of fellowship before obtaining employment. Stratification of the data by regions of the country or by the size of the residency programs does not show large differences. The data also indicate a high percentage of employment for graduates of pathology residency programs and a stable job market over the years covered by the surveys. © The Author(s) 2020.Advances in actuating fabrics can enable a paradigm shift in the field of smart wearables by dynamically fitting themselves to the unique topography of the human body. selleck inhibitor Applications including soft wearable robotics, continuous health monitoring, and body-mounted haptic feedback systems are dependent upon simultaneous body proximity and garment stiffness for functionality. Passive fabrics and fitting mechanisms are unable to conform around surface concavities and require either high elasticity or a multiplicity of closure devices to achieve garment fit. The design, manufacture, and validation of the first circumferentially contractile and topographic self-fitting garments composed of NiTi-based shape memory alloy (SMA) knitted actuators that dynamically conform to the unique shape and size of the wearer's body in response to a change of the garment's temperature is introduced. Advanced materials and systems innovations 1) enable novel garment manufacturing and application strategies, 2) facilitate topographical fitting (spatial actuation) through garment architectural design, and 3) provide tunable NiTi-based SMA actuation temperatures to enable actuation on the surface of human skin.
Homepage: https://www.selleckchem.com/products/crt-0105446.html
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