Publications by authors named "John Ronald"
Fluorine-19 (F) MRI has become an established tool for in vivo cell tracking following ex vivo or in vivo labelling of various cell types with F perfluorocarbons (PFCs). Here, we developed and evaluated novel mouse-specific radiofrequency (RF) hardware for improved dual H anatomical imaging and deep tissue F MR detection of PFCs. Three linearly polarized birdcage RF coils were constructed-a dual-frequency H/F coil, and a pair of single-frequency H and F coils, designed to be used sequentially.
View Article and Find Full Text PDFPannexin 1 (PANX1) is upregulated in many cancers, where its activity and signalling promote tumorigenic properties. Here, we report a novel ∼25 kDa isoform of human PANX1 (hPANX1-25K) which lacks the N-terminus and was detected in several human cancer cell lines including melanoma, osteosarcoma, breast cancer and glioblastoma multiforme. This isoform was increased upon CRISPR/Cas9 deletion targeting the first exon near M1, suggesting a potential alternative translation initiation (ATI) site.
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- Cell therapies using mesenchymal stromal cells (MSCs), particularly human adipose-derived stromal cells (hASCs), are gaining attention as potential treatments for peripheral arterial disease (PAD) and critical limb ischemia (CLI), focusing on their ability to promote blood vessel growth.
- This study examined the effects of different natural polysaccharide hydrogels, specifically methacrylated glycol chitosan (MGC) and methacrylated hyaluronic acid (MHA), on the survival and pro-angiogenic functions of hASCs when encapsulated within them.
- Results showed that while hASCs maintained high viability in both hydrogels, those in MGC hydrogels secreted more pro-
Article Synopsis
- * CRISPR base editors, specifically adenine and cytosine base editors, can accurately alter DNA but face challenges with delivery efficiency and safety when using viral vectors.
- * This study introduces non-viral minicircles as a new delivery method for base editors, showing improved gene expression and luminescence signals compared to controls, and sets the stage for future research in cancer models.
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- This study focuses on the development of HER2-targeted chimeric antigen receptor natural killer (CAR-NK) cells as a potential therapy for ovarian cancer, offering a less complex and more cost-effective alternative to traditional CAR T cell therapies.
- CAR-NK cells were genetically modified to express both a HER2-targeted CAR and a PET reporter gene, allowing for better tracking and imaging of these immune cells after administration.
- Experimental results demonstrated that CAR-NK cells were more effective in killing cancer cells, reducing tumor size and improving survival in mice, while also allowing for successful monitoring through bioluminescence and PET imaging techniques.
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- Cancer remains a serious global health challenge, and theranostics is a promising approach that merges diagnostic tools with personalized treatment strategies.
- The review covers the evolution of theranostics in oncology, discussing key developments over the last decade such as targeted drug delivery and advances in imaging, molecular biology, and nanomedicine.
- It highlights how these innovations improve diagnostic accuracy and enable tailored therapies for patients, while also addressing future challenges and potential advancements in the field.
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- Cellular immunotherapy, particularly CAR T cell therapy, has seen advancements in treating cancers, but patient responses vary, and some tumors remain resistant.
- Researchers developed a synthetic Notch (synNotch) receptor to create a blood test that signals intratumoral interactions between engineered immune cells and cancer cells via secreted embryonic alkaline phosphatase (SEAP).
- The new system successfully demonstrated that the presence of CD19 in tumors leads to detectable SEAP levels in the blood, offering a potential method for monitoring immune responses in cancer therapies.
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- Five amphiphilic, anionic Mn(II) complexes were created to be used as contrast agents for liver MRI, targeting specific transporters in the body.
- The complexes were synthesized in three steps from a common chelator, showing relaxivity values between 2.3 and 3.0 mM s in a buffered saline solution.
- In vivo studies in mice and in vitro assays with human cell lines demonstrated effective uptake of these complexes, suggesting they could be adapted for various MRI applications.
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- Duchenne muscular dystrophy (DMD) is a serious neuromuscular disorder caused by the loss of dystrophin, leading to severe muscle degeneration and premature death, often from heart or respiratory failure.
- Innovative treatments have improved life expectancy for DMD patients but have also resulted in increased late-onset heart failure and cognitive decline, necessitating better assessment methods of related heart and brain issues.
- The study introduces a TSPO-PET imaging protocol to investigate inflammation in the hearts and brains of a dystrophin-deficient mouse model, showing significant increased activity in these areas, which could help evaluate the effects of neuroinflammation alongside cardiac issues in DMD.
. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation.
View Article and Find Full Text PDFVisualizing cell-cell communication using synthetic notch activated MRI.
Proc Natl Acad Sci U S A
March 2023
Article Synopsis
- Cell-cell communication is crucial for multicellular organisms, and engineered immune cells can be used in cancer immunotherapies by targeting specific cancer antigens to kill tumors.
- Researchers used a synthetic Notch system to create T cells that express optical and MRI reporter genes when they interact with CD19 on cancer cells, allowing for detailed imaging of these interactions in tumor-bearing mice.
- The same technology was applied to human NK-92 cells, demonstrating their ability to be tracked in cancer models, suggesting this imaging approach could enhance the monitoring of cell therapies and improve our understanding of immune interactions in health and disease.
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- - Magnetic particle imaging (MPI) and bioluminescence imaging (BLI) are combined to track cancer cell activity and assess cell viability in mice, specifically using Akaluc-expressing 4T1Br5 cells labeled with superparamagnetic iron oxide nanoparticles (SPIO).
- - The study showed that BLI indicated tumor growth over time, while MPI revealed a decrease in signal due to SPIO dilution as the tumor grew, allowing insights into tumor dynamics and cell behavior.
- - This multimodal imaging technique provides a more comprehensive understanding of cancer cell fate, supporting better evaluation of treatment methods and metastatic mechanisms.
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- Stem cell therapies have great potential for treating various diseases, and tracking their location and viability after being administered is crucial for assessing patient responses and side effects.
- This study focused on engineering mesenchymal stem cells (MSCs) with a PET reporter gene and magnetic nanoparticles to enable imaging through different methods, including MPI and BLI, over a 30-day period in mice.
- The findings revealed that while MPI was effective for early detection of MSCs, PET provided a clearer signal for tracking these cells over a longer duration, highlighting the benefits of using both imaging techniques together for comprehensive monitoring.
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- Metastasis is a major cause of cancer deaths, but it's not well-studied, often due to a lack of tools to accurately track it in living organisms.
- The study developed an imaging system using an MRI reporter gene (oatp1b3) to enable high-resolution, 3D tracking of cancer cells in live mice.
- This new system allows researchers to visualize and monitor the spread of metastases in real time, including detection of tiny clusters of cancer cells in the lungs, thus enhancing metastasis research significantly.
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- The use of gadolinium-based contrast agents (GBCAs) is controversial, but Gd(III)-EOB-DTPA is still favored for its unique imaging capabilities related to the liver.
- Researchers developed a new liver-specific MRI probe called Mn(III)TriCP-PhOEt, which demonstrated higher relaxivity compared to Gd(III)-EOB-DTPA and specifically targets liver cells through Oatp1 channels.
- In experiments with mice, Mn(III)TriCP-PhOEt significantly enhanced liver imaging results and showed promise as an effective probe for in vivo studies.
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- Nucleic acids have great potential in treating diseases, but require delivery vehicles to enter cells, with polycations forming polyplexes for transport while balancing cell toxicity.
- The study introduces a new self-immolative polyglyoxylamide (PGAm) platform that uses multivalent interactions to effectively deliver nucleic acids and releases them through depolymerization under mildly acidic conditions.
- Results show that this PGAm system exhibits lower cytotoxicity compared to traditional agents like jetPEI, while achieving similar levels of reporter gene expression, indicating a promising approach for nucleic acid delivery.
Article Synopsis
- The study aimed to create a dual MRI/PET reporter gene system to improve tracking and imaging of transplanted engineered cells in the body, combining the strengths of both imaging techniques.
- Researchers engineered breast cancer cells to express two specific human genes that allow for the uptake of an MRI contrast agent and a PET tracer, enabling simultaneous imaging.
- Results showed that the engineered tumors had significantly higher signals in both MRI and PET imaging compared to normal tumors, allowing for better visualization and tracking of these cells.
Article Synopsis
- CAR T cell therapies have shown success in treating blood cancers but face challenges, including variable patient responses and side effects, particularly in treating solid tumors.
- A new imaging technique using Fluorine-19 MRI aims to visualize CAR-T cells labeled with perfluorocarbon, which could help assess treatment effectiveness and monitor safety.
- The study involved injecting PFC+ CAR-T cells into leukemia-affected mice, with results showing successful detection of these cells and a significant reduction in tumor burden compared to untreated mice by 14 days post-treatment.
Article Synopsis
- Bioluminescence imaging (BLI) utilizes luciferase reporters to visualize cells and biochemical processes noninvasively in living animals, particularly in rodent models for disease research and therapy evaluation.
- Despite its usefulness, BLI faces challenges such as low light output and the absorption of light by tissues, which limit its effectiveness for detecting small cell populations in deeper areas and for use in larger animals.
- Recent advances in luciferase technology aim to enhance the sensitivity of BLI, broadening its potential applications in biological research.
Molecular imaging of cellular immunotherapies in experimental and therapeutic settings.
Cancer Immunol Immunother
June 2022
Cell-based cancer immunotherapies are becoming a routine part of the armamentarium against cancer. While remarkable successes have been seen, including durable remissions, not all patients will benefit from these therapies and many can suffer from life-threatening side effects. These differences in efficacy and safety across patients and across tumor types (e.
View Article and Find Full Text PDFThere is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumor behavior, and metastatic properties observed in the original tumor. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metsastases and validate this method with imaging during tumor development.
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- Synchronous bilateral breast cancer (SBBC) is characterized by cancer in both breasts, leading to increased metastatic rates and lower survival compared to unilateral cases; a new preclinical model was developed for studying SBBC.
- Researchers used bioluminescence and fluorescence imaging techniques to analyze cancer cell behavior in mice, discovering that metastasis in the lungs began around day 28 and involved contributions from both primary tumors.
- Findings suggest a significant level of cancer cell mixing from both tumors may accelerate metastasis and complicate treatment, emphasizing the need for better understanding and planning of SBBC therapies.
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- Researchers created a new 3-D bioscaffold using a "cell-assembly" method composed of decellularized adipose tissue (DAT) beads, aimed at enhancing soft tissue regeneration with high densities of human adipose-derived stromal cells (ASCs).
- In vitro tests showed that the ASCs effectively remodeled the scaffold’s extracellular matrix, maintaining their viability for over a week, especially with growth factor preconditioning that improved scaffold stability.
- In vivo studies indicated that the ASC delivery in the new cell-assembled scaffolds showed better initial cell tracking and enhanced endothelial cell infiltration, suggesting a more stable vascular network compared to traditional methods.
Article Synopsis
- - The NIH Somatic Cell Genome Editing Consortium aims to enhance human health by developing safer and more effective genome editing techniques for treating diseases directly in patients' cells.
- - The consortium plans to create a toolkit that includes new genome editing technologies, delivery methods, and validated data, which will be shared with the biomedical research community.
- - By conducting thorough testing and validation, the initiative seeks to accelerate the discovery of new therapies for various health conditions.
Article Synopsis
- Recent advancements have allowed circulating tumor cells (CTCs) to be engineered for targeted therapy in cancer treatment due to their ability to home in on tumors.* -
- The study explored using magnetic particle imaging (MPI) to detect these iron-labeled CTCs in a mouse model of breast cancer, offering a sensitive imaging method.* -
- This research successfully demonstrated that MPI can effectively visualize the self-homing behavior of CTCs in tumors, establishing a new approach for tracking cancer cells in vivo.*