Publications by authors named "Megan Madonna"

Purpose: The purpose of this systematic review and meta-analysis was to synthesise the evidence from randomised controlled trials for caregiver training on child and family outcomes for children with paediatric feeding disorder.

Method: A systematic review was conducted in accordance with PRISMA guidelines. Searches of Medline, CINAHL, PsychInfo, and EMBASE were conducted using the key concepts of paediatrics, feeding disorders, parents/caregivers, and training.

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Fewer than 20% of triple-negative breast cancer patients experience long-term responses to mainstay chemotherapy. Resistant tumor subpopulations use alternative metabolic pathways to escape therapy, survive, and eventually recur. Here, we show in vivo, longitudinal metabolic reprogramming in residual disease and recurrence of triple-negative breast cancer xenografts with varying sensitivities to the chemotherapeutic drug paclitaxel.

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After an initial response to chemotherapy, tumor relapse is frequent. This event is reflective of both the spatiotemporal heterogeneities of the tumor microenvironment as well as the evolutionary propensity of cancer cell populations to adapt to variable conditions. Because the cause of this adaptation could be genetic or epigenetic, studying phenotypic properties such as tumor metabolism is useful as it reflects molecular, cellular, and tissue-level dynamics.

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Article Synopsis
  • Recurrent cancer cells are a major cause of death in breast cancer, especially in patients with high Her2 expression.
  • This study investigates the metabolic changes in breast tumors as they transition through regression, dormancy, and recurrence, using imaging techniques to track energy production shifts.
  • Fast-recurrence tumors change their energy source from glucose to fatty acids, and treatment with a fatty acid inhibitor can enhance glucose uptake and prolong survival, highlighting the importance of timing for effective therapy.
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Aggressive breast cancer has been shown to shift its metabolism towards increased lipid catabolism as the primary carbon source for oxidative phosphorylation. In this study, we present a technique to longitudinally monitor lipid metabolism and oxidative phosphorylation in pre-clinical tumor models to investigate the metabolic changes with mammary tissue development and characterize metabolic differences between primary murine breast cancer and normal mammary tissue. We used optical spectroscopy to measure the signal of two simultaneously injected exogenous fluorescent metabolic reporters: TMRE (oxidative phosphorylation surrogate) and Bodipy FL C16 (lipid catabolism surrogate).

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Redox metabolism plays essential functions in the pathology of cancer and many other diseases. While several radiotracers for imaging redox metabolism have been developed, there are no reports of radiotracers for in vivo imaging of protein oxidation. Here we take the first step towards this goal and describe the synthesis and kinetic properties of a new positron emission tomography (PET) [F]Fluoro-DCP radiotracer for in vivo imaging of protein sulfenylation.

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Targeting a tumor's metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients.

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With the large number of women diagnosed and treated for breast cancer each year, the importance of studying recurrence has become evident due to most deaths from breast cancer resulting from tumor recurrence following therapy. To mitigate this, cellular and molecular pathways used by residual disease prior to recurrence must be studied. An altered metabolism has long been considered a hallmark of cancer, and several recent studies have gone further to report metabolic dysfunction and alterations as key to understanding the underlying behavior of dormant and recurrent cancer cells.

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Therapeutically exploiting vascular and metabolic endpoints becomes critical to translational cancer studies because altered vascularity and deregulated metabolism are two important cancer hallmarks. The metabolic and vascular phenotypes of three sibling breast tumor lines with different metastatic potential are investigated in vivo with a newly developed quantitative spectroscopy system. All tumor lines have different metabolic and vascular characteristics compared to normal tissues, and there are strong positive correlations between metabolic (glucose uptake and mitochondrial membrane potential) and vascular (oxygen saturations and hemoglobin concentrations) parameters for metastatic (4T1) tumors but not for micrometastatic (4T07) and nonmetastatic (67NR) tumors.

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The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in models of diabetic peripheral arterial disease (PAD) and mechanically induced post-traumatic osteoarthritis (PTOA). PPS-MS (∼1 m diameter) significantly scavenged hydrogen peroxide (HO), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell-based assays. Elevated ROS levels (specifically HO) were confirmed in both a mouse model of diabetic PAD and in a mouse model of PTOA, with greater than 5- and 2-fold increases in HO, respectively.

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While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability.

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Manual and automated methods were compared for routine screening of compounds for antimicrobial activity. Automation generally accelerated assays and required less user intervention while producing comparable results. Automated protocols were validated for planktonic, biofilm, and agar cultures of the oral microbe Streptococcus mutans that is commonly associated with tooth decay.

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