Publications by authors named "Wade Koba"

Radiation-induced lung injury (RILI) initiates radiation pneumonitis and progresses to fibrosis as the main side effect experienced by patients with lung cancer treated with radiotherapy. There is no effective drug for RILI. Sustained vascular activation is a major contributor to the establishment of chronic disease.

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  • - The study investigates the effects of ultrahigh dose-rate FLASH proton therapy on gastrointestinal injury, highlighting that while FLASH therapy aims to reduce normal tissue toxicity, it showed significantly reduced survival rates in mice compared to conventional therapy.
  • - Whole abdominal irradiation was conducted on mice, using both FLASH and conventional proton therapy, and survival rates were assessed, along with intestinal histology analysis through a new AI-based technique.
  • - Results indicated that despite enhanced dose rates with FLASH therapy, there was no significant improvement in gut cell regeneration or histology at 4 days post-irradiation, raising questions about FLASH's efficacy for gastrointestinal sparing.
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  • Vitamin D deficiency is widespread, particularly affecting women of childbearing age, and can increase the risk of immune problems in their children later in life.
  • The study investigates how prenatal vitamin D deficiency impacts the immune cell makeup in offspring through experiments with vitamin D-deficient mice and analysis of data from 75 healthy pregnant women.
  • Results show that low maternal vitamin D levels lead to changes in immune cell proportions in offspring, suggesting that the body retains a "memory" of prenatal vitamin D deficiency that affects immune development throughout life.
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Haematopoietic stem cells (HSCs) reside in specialized microenvironments, also referred to as niches, and it has been widely believed that HSC numbers are determined by the niche size alone . However, the vast excess of the number of niche cells over that of HSCs raises questions about this model. We initially established a mathematical model of niche availability and occupancy, which predicted that HSC numbers are restricted at both systemic and local levels.

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Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, exactly how the body remembers exposure to an adverse environment during development is poorly understood.

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Unlabelled: Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects.

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  • Pancreatic ductal adenocarcinoma (PDAC) is difficult to treat due to its ability to evade immune responses, but a new microbiome-based therapy shows promise by introducing a tetanus toxoid protein into tumor cells, reactivating existing T cell responses.
  • In mouse models, this treatment led to the accumulation of the tetanus protein in tumors, recruitment of CD4 T cells, and the production of immune molecules that help kill tumor cells, especially when combined with low doses of gemcitabine (GEM).
  • The combination treatment significantly reduced tumor size (by 80%) and metastases (by 87%), while increasing survival rates in treated mice, suggesting this approach could be a viable alternative for
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Patients with KRAS mutated colorectal cancer (CRC) represent a cohort with unmet medical needs, with limited options of FDA-approved therapies. Representing 40-45% of all CRC patients, they are considered ineligible to receive anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Although several mouse models of CRC have been developed during the past decade, one genetically resembling the KRAS mutated CRC is yet to be established.

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Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers.

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Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient. Listeria-32P kills tumor cells through both 32P-induced ionizing radiation and Listeria-induced reactive oxygen species (ROS).

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Background: Trypanosoma cruzi, the causative agent of Chagas disease, has high affinity for lipoproteins and adipose tissue. Infection results in myocarditis, fat loss and alterations in lipid homeostasis. This study was aimed at analyzing the effect of high fat diet (HFD) on regulating acute T.

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Background: Novel approaches to treatment of pancreatic cancer (PCa) are urgently needed. A chimeric monoclonal antibody (mAb) chTNT3 binds to single-strand DNA (ssDNA) and RNA released from the non-viable cells in fast growing tumors. Here the authors investigated whether radioimmunotherapy (RIT) using chTNT3 mAb radiolabeled with 213-Bismuth ((213)Bi) could be effective in treatment of experimental PCa.

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The scientific study of living animals may be dated to Aristotle's original dissections, but modern animal studies are perhaps a century in the making, and advanced animal imaging has emerged only during the past few decades. In vivo imaging now occupies a growing role in the scientific research paradigm. Imaging of small animals has been particularly useful to help understand human molecular biology and pathophysiology using rodents, especially using genetically engineered mice (GEM) with spontaneous diseases that closely mimic human diseases.

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Bisected, complex N-glycans on glycoproteins are generated by the glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins. Previously, we showed that MGAT3 reduces growth factor signaling and retards mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter. However, the penetrance of the tumor phenotype became variable in mixed FVB/N and C57BL/6 female mice and we therefore investigated a congenic C57BL/6 Mgat3(-/-)/MMTV-PyMT model.

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Background: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi), is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited.

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For the greater part of the last century, basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination from suitable animal models of disease. In the last three decades, however, new techniques have been developed that permit the imaging of live animals using X-rays, radiotracer emissions, magnetic resonance signals, sound waves and optical fluorescence, and bioluminescence. The objective of this review is to provide a broad overview of common animal imaging modalities, with a focus on positron emission tomography (PET), single photon emission computed tomography (SPECT), and computed tomography (CT).

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Background: Pasireotide (SOM230), a long-acting somatostatin analogue (LAR), has improved agonist activity at somatostatin receptors. We tested the effect of SOM230 on insulin secretion, serum glucose concentrations, tumor growth, and survival using an MEN1 transgenic mouse model.

Methods: Eight 12-month-old conditional Men1 knockout mice with insulinoma were assessed.

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The KCNQ1 α subunit and the KCNE2 β subunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography.

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Imaging devices for small animals have emerged in the past 10 years as extraordinarily useful tools in translational research and drug development. The Food and Drug Administration requires animal testing after in vitro drug discovery but before human application. Many small animal instruments have been developed in analogy to human scale devices, including positron emission tomography, single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and ultrasound.

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Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T.

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Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16(Ink4a) and p21(CIP).

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Scedosporium apiospermum is part of the Pseudallescheria-Scedosporium complex. Peptidorhamnomannans (PRMs) are cell wall glycopeptides present in some fungi, and their structures have been characterized in S. apiospermum, S.

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Noninvasive assessment of cardiac structure and function is essential to understand the natural course of murine infection with Trypanosoma cruzi. Magnetic resonance imaging (MRI) and echocardiography have been used to monitor anatomy and function; positron emission tomography (PET) is ideal for monitoring metabolic events in the myocardium. Mice infected with T.

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Thyroid dysfunction is a global health concern, causing defects including neurodevelopmental disorders, dwarfism and cardiac arrhythmia. Here, we show that the potassium channel subunits KCNQ1 and KCNE2 form a thyroid-stimulating hormone-stimulated, constitutively active, thyrocyte K+ channel required for normal thyroid hormone biosynthesis. Targeted disruption of Kcne2 in mice impaired thyroid iodide accumulation up to eightfold, impaired maternal milk ejection, halved milk tetraiodothyronine (T4) content and halved litter size.

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Purpose: Measured cardiac [F]-2-fluoro-2-deoxyglucose (FDG) activity in human PET scans is variable despite efforts to standardize patient preparation. Heart uptake can obscure chest disease, and is of physiologic interest. Short-term carbohydrate (CHO) restriction can reduce FDG uptake, although unreliably, whereas long-term restriction of CHO has not been systematically studied.

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