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small molecule imaging

Roberto A Salas Fragomeni, Tali Amir, Sara Sheikhbahaei, Susan C Harvey, Mehrbod S Javadi, Lilja Solnes, Ana Kiess, Mohamad E Allaf, Martin Pomper, Michael A Gorin, Steven P Rowe
Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly overexpressed on prostate cancer epithelial cells and for which there is a growing body of literature examining the role of small molecule and antibody radiotracers targeted against this protein for prostate cancer detection and therapy. Despite its name, PSMA is also expressed, to varying degrees, in the neovasculature of a wide variety of non-prostate cancers; indeed, the pathology literature is replete with promising immunohistochemistry findings...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Shyam Nyati, Nauman Chaudhry, Areeb Chatur, Brandon S Gregg, Lauren Kimmel, Dheeraj Khare, Venkatesha Basrur, Dipankar Ray, Alnawaz Rehemtulla
Post-translational K63-linked poly-ubiquitination of AKT is required for its membrane recruitment and phosphorylation dependent activation in response to growth-factor stimulation. Current assays for target specific poly-ubiquitination involve cumbersome enzymatic preparations and semi-quantitative readouts. We have engineered a reporter that can quantitatively and in a target specific manner report on AKT-directed K63-polyubiquitination (K63UbR) in live cells. The reporter constitutes the AKT-derived poly-ubiquitination substrate peptide, a K63 poly-ubiquitin binding domain (UBD) as well as the split luciferase protein complementation domains...
February 16, 2018: Oncotarget
Junwei Shi, Thirupandiyur S Udayakumar, Keying Xu, Nesrin Dogan, Alan Pollack, Yidong Yang
PURPOSE: The image guided small animal arc radiation treatment platform has adopted onboard cone beam computed tomography and bioluminescence tomography (BLT). We used BLT to guide irradiation delivery and quantitatively assess irradiation-induced tumor response. METHODS AND MATERIALS: BLT was first validated on a tissue-simulating phantom, where the internal chemiluminescent liquid had a constant volume while its luminescence intensity gradually decayed. Then, in vivo experiments were performed on BALB/c mice orthotopically inoculated with 4T1 breast carcinoma cells expressing luciferase...
February 2, 2018: International Journal of Radiation Oncology, Biology, Physics
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio Ivan Wistuba
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches. MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
March 8, 2018: Journal of Thoracic Oncology
Hailey J Knox, Tae Wook Kim, Zhouyang Zhu, Jefferson Chan
Hypoxia results when the oxygen supply to rapidly growing tumors becomes inadequate to support various physiological processes. This plays a role in tumor metastasis and treatment resistance. Therefore, identifying tumor hypoxia can guide treatment planning and predict patient responses. However, hypoxic volumes are heterogeneously dispersed throughout a tumor, making it a challenge to pinpoint them with any degree of accuracy. Herein, we report the development of ratiometric hypoxia probe 1 (rHyP-1), which is a hypoxia-responsive small-molecule probe designed for reliable hypoxia detection using photoacoustic imaging...
March 9, 2018: ACS Chemical Biology
Lili Guo, Lin Li, Meiying Liu, Qing Wan, Jianwen Tian, Qiang Huang, Yuanqing Wen, Shangdong Liang, Xiaoyong Zhang, Yen Wei
Carbon quantum dots (CDs) have standout as one of the most important carbon nanomaterials owing to their small size, optical properties, biocompatibility and low toxicity. These CDs have been extensively explored for various applications especially in the biomedical fields. Although great efforts have been devoted to the fabrication of CDs through both top-down and bottom-up methods, most of these CDs exhibited blue emission under UV light irradiation. In this work, we reported a novel, green, economic approach for preparation of nitrogen doped CDs by directly microwave-assisted heating small organic molecules at 120°C for 5min using Glu and amino group of MPD as the precursors and ethylene glycol as solvent...
March 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Christopher R Hackley, Esteban O Mazzoni, Justin Blau
Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMPr in bacteria and embryonic stem cells and validated the sensor in mammalian neurons in vitro and in Drosophila circadian pacemaker neurons in intact brains. Comparison with other single-wavelength cAMP sensors showed that cAMPr improved the quantitative detection of cAMP abundance...
March 6, 2018: Science Signaling
Ján Kozempel, Olga Mokhodoeva, Martin Vlk
This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like211 At,223 Ra,225 Ac/213 Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging...
March 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yuxi Liu, Shane Gonen, Tamir Gonen, Todd O Yeates
Current single-particle cryo-electron microscopy (cryo-EM) techniques can produce images of large protein assemblies and macromolecular complexes at atomic level detail without the need for crystal growth. However, proteins of smaller size, typical of those found throughout the cell, are not presently amenable to detailed structural elucidation by cryo-EM. Here we use protein design to create a modular, symmetrical scaffolding system to make protein molecules of typical size suitable for cryo-EM. Using a rigid continuous alpha helical linker, we connect a small 17-kDa protein (DARPin) to a protein subunit that was designed to self-assemble into a cage with cubic symmetry...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Zhengtian Song, Sreya Sarkar, Andrew D Vogt, Gerald D Danzer, Casey J Smith, Ellen J Gualtieri, Garth J Simpson
The low limits of detection afforded by second harmonic generation (SHG) microscopy coupled with image analysis algorithms enabled quantitative modeling of the temperature-dependent crystallization of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs). ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. Extensive stability testing is typically performed for ASD characterization, the time-frame for which is often dictated by the earliest detectable onset of crystal formation...
March 5, 2018: Analytical Chemistry
Michael Gotrik, Gurpreet Sekhon, Saumya Saurabh, Margaret Nakamoto, Michael Eisenstein, H Tom Soh
RNA aptamers that generate a strong fluorescence signal upon binding a nonfluorescent small-molecule dye offer a powerful means for the selective imaging of individual RNA species. Unfortunately, conventional in vitro discovery methods are not efficient at generating such fluorescence-enhancing aptamers, because they primarily exert selective pressure based on target affinity-a characteristic that correlates poorly with fluorescence enhancement. Thus, only a handful of fluorescence-enhancing aptamers have been reported to date...
March 5, 2018: Journal of the American Chemical Society
Leonel Malacrida, Estella Rao, Enrico Gratton
Image correlation analysis has evolved to become a valuable method of analysis of the diffusional motion of molecules in every points of a live cell. Here we compare the iMSD and the 2D-pCF approaches that provide complementary information. The iMSD method provides the law of diffusion and it requires spatial averaging over a small region of the cell. The 2D-pCF does not require spatial averaging and it gives information about obstacles for diffusion at pixel resolution. We show the analysis of the same set of data by the two methods to emphasize that both methods could be needed to have a comprehensive understanding of the molecular diffusional flow in a live cell...
February 28, 2018: Methods: a Companion to Methods in Enzymology
Somayeh Vandghanooni, Morteza Eskandani, Jaleh Barar, Yadollah Omidi
The side effects of chemotherapeutics during the course of cancer treatment limit their clinical outcomes. The most important mission of the modern cancer therapy modalities is the delivery of anticancer drugs specifically to the target cells/tissue in order to avoid/reduce any inadvertent non-specific impacts on the healthy normal cells. Nanocarriers decorated with a designated targeting ligand such as aptamers (Aps) and antibodies (Abs) are able to deliver cargo molecules to the target cells/tissue without affecting other neighboring cells, resulting in an improved treatment of cancer...
February 27, 2018: European Journal of Pharmaceutical Sciences
Fabio Cerignoli, Yama A Abassi, Brandon J Lamarche, Garret Guenther, David Santa Ana, Diana Guimet, Wen Zhang, Jing Zhang, Biao Xi
A growing understanding of the molecular interactions between immune effector cells and target tumor cells, coupled with refined gene therapy approaches, are giving rise to novel cancer immunotherapeutics with remarkable efficacy in the clinic against both solid and liquid tumors. While immunotherapy holds tremendous promise for treatment of certain cancers, significant challenges remain in the clinical translation to many other types of cancers and also in minimizing adverse effects. Therefore, there is an urgent need for functional potency assays, in vitro and in vivo, that could model the complex interaction of immune cells with tumor cells and can be used to rapidly test the efficacy of different immunotherapy approaches, whether it is small molecule, biologics, cell therapies or combinations thereof...
2018: PloS One
Andrew J Shepherd, Aaron D Mickle, Suraj Kadunganattil, Hongzhen Hu, Durga P Mohapatra
Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment...
2018: Frontiers in Cellular Neuroscience
Fan Zhang, Benhao Li, Lingfei Lu, Mengyao Zhao, Zuhai Lei
A novel small molecule fluorophore FD-1080 with both excitation and emission in NIR-II region has been successfully synthesized for in vivo imaging. A heptamethine structure is designed to shift the absorption and emission into NIR-II region. Sulphonic group and cyclohexene group are introduced to enhance its water solubility and stability. The quantum yield of FD-1080 is 0.31 %, and can be increased to 5.94 % after combining with fetal bovine serum (FBS). Significantly, 1064 nm NIR-II excitation was demonstrated with the high tissue penetration depth and superior imaging resolution compared to previously reported NIR excitation from 650 nm to 980 nm...
March 1, 2018: Angewandte Chemie
Chen Chen, Shenfei Zong, Zhuyuan Wang, Ju Lu, Dan Zhu, Yizhi Zhang, Ruohu Zhang, Yiping Cui
Exosomes are small membrane vesicles secreted by a wide variety of cells. Studies have demonstrated that exosomal miRNAs can influence the biological processes of recipient cells. Therefore, direct imaging and tracking of exosomal miRNAs in living recipient cells are essential for exosome functional analysis. However, the moderate spatial resolution of conventional fluorescence microscopy limits the precise imaging and tracking of exosomes considering their relatively small size (<100 nm). Here, we took advantage of single molecule localization microscopy (SMLM) to realize the visualization and dynamic tracking of exosomes and exosomal miRNAs in living cells...
March 1, 2018: Nanoscale
Yan Li, Yanhui Li, Weihong Ji, Zhiguo Lu, Linying Liu, Yuanjie Shi, Guanghui Ma, Xin Zhang
Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs)...
February 27, 2018: Journal of the American Chemical Society
Marion David, Pascaline Lécorché, Maxime Masse, Aude Faucon, Karima Abouzid, Nicolas Gaudin, Karine Varini, Fanny Gassiot, Géraldine Ferracci, Guillaume Jacquot, Patrick Vlieghe, Michel Khrestchatisky
Insufficient membrane penetration of drugs, in particular biotherapeutics and/or low target specificity remain a major drawback in their efficacy. We propose here the rational characterization and optimization of peptides to be developed as vectors that target cells expressing specific receptors involved in endocytosis or transcytosis. Among receptors involved in receptor-mediated transport is the LDL receptor. Screening complex phage-displayed peptide libraries on the human LDLR (hLDLR) stably expressed in cell lines led to the characterization of a family of cyclic and linear peptides that specifically bind the hLDLR...
2018: PloS One
Limin Zhang, Yang Tian
The in vivo analysis of chemical signals in brain extracellular fluid (ECF) using implanted electrochemical biosensors is a vital way to study brain functions and brain activity mapping. This approach offers excellent spatial (10-200 μm) and temporal (approximately second) resolution and the major advantage of long-term stability. By implantation of a microelectrode in a specific brain region, changes in the concentration of a variety of ECF chemical species can be monitored through applying a suitable electrical signal and, typically, recording the resulting Faradaic current...
February 27, 2018: Accounts of Chemical Research
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