A5070894504- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Breast Cancer Treatment Studies
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Effects of Radiation Exposure
- BRCA gene mutations in cancer
- Molecular Biology Techniques and Applications
- Lung Cancer Research Studies
- Prostate Cancer Treatment and Research
- Cancer Treatment and Pharmacology
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Chromatin Dynamics
- Radiopharmaceutical Chemistry and Applications
- Cell death mechanisms and regulation
- X-ray Diffraction in Crystallography
- Electrochemical Analysis and Applications
- Circular RNAs in diseases
- Ultrasound and Hyperthermia Applications
- Radiation Therapy and Dosimetry
- Neuroendocrine Tumor Research Advances
- RNA Research and Splicing
- Crystallization and Solubility Studies
- Glutathione Transferases and Polymorphisms
University of Michigan
2019-2025
Calvin University
2016-2019
Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use radiation therapy (RT); therefore, approaches that result radiosensitization BC critically needed. Using patients' tumor gene expression data from 4 independent sets, we correlated to find genes significantly early after RT. The highest-ranked gene, TTK, was most highly expressed across multiple sets. Inhibition TTK by both genetic and pharmacologic methods enhanced...
Abstract Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), local rates 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there clear need intensification therapy, including radiation. Inhibition DNA repair protein PARP1 has had little efficacy as single agent outside studies restricted to BRCA mutations; however, inhibition (PARPi) may lead radiosensitization aggressive tumor types. Thus, this study...
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor-positive (ER+) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy multiple preclinical cancer models.Transcriptomic proteomic analyses were used identify significantly altered pathways after CDK4/6i. Clonogenic assays quantify enhancement ratio (rER). DNA damage was...
Background: Due to the lack of molecular-targeted therapies for triple-negative breast cancer (TNBC), there have been efforts use multimodal strategies enhance efficacy existing such as radiation. The androgen receptor (AR) has identified a radiosensitizing target and is expressed in 25-50% TNBC tumors. combination AR inhibitors, enzalutamide (enza), radiation therapy (RT), leads radiosensitization AR+ models but mechanism by which mediates radioresistance not known, targeting this could...
Abstract Background: Breast cancer (BC), the most common globally and a leading cause of death in women, often utilizes radiation therapy (RT) as part treatment, with over 85% patients receiving RT after breast-conserving surgery. Still, 15% women experience local recurrence despite RT, underscoring need to better understand molecular mechanisms driving response resistance. We hypothesized that transcriptomic changes occur ionizing intrinsically radiosensitive resistant BC models would offer...
Increased rates of locoregional recurrence (LR) have been observed in triple negative breast cancer (TNBC) despite multimodality therapy, including radiation (RT). Recent data suggest inhibiting the androgen receptor (AR) may be an effective radiosensitizing strategy, and AR is expressed 15-35% TNBC tumors. The aim this study was to determine whether seviteronel (INO-464), a novel CYP17 lyase inhibitor antagonist, able radiosensitize AR-positive (AR+) models. In cell viability assays,...
Standard radiation therapy (RT) does not reliably provide locoregional control for women with multinode-positive breast cancer and triple-negative (TNBC). We hypothesized that CDK4/6 inhibition (CDK4/6i) would increase the radiosensitivity only of estrogen receptor-positive (ER+) cells, but also TNBC expresses retinoblastoma (RB) protein. found CDK4/6i radiosensitized RB WT (n = 4, enhancement ratio [rER]: 1.49-2.22) failed to radiosensitize RB-null 3, rER: 0.84-1.00). expression predicted...
Abstract Endocrine therapy (ET) is an effective first-line for women with estrogen receptor-positive (ER + ) breast cancers. While both ionizing radiation (RT) and ET are used the treatment of ER+ cancer, most sequencing effect on tumor radiosensitization remains unclear. Here we sought to understand effects inhibiting receptor (ER) signaling in combination RT multiple preclinical cancer models. Clonogenic survival assays were performed using variable pre- post-treatment conditions assess...
Monte Carlo simulations on UV‐vis titration data quantify how the precision of binding constant calculation deteriorates in strong regimes. For 1:1 binding, global analysis is reliable when K [H] o < 1000, a significant improvement over previous recommendations. Initial concentration error generates majority calculated constant. We derive novel experimental design formula to maximize both and weak regimes validate it through simulations.
Making optimal pedagogical and predictive use of the radius ratio rule to distinguish between solid state structures that feature tetrahedral, octahedral cubic holes requires several updated insights. A comparative analysis Born–Landé equation for lattice energy is developed show rock salt structure a suitable choice ratios 0.326 1.00. The lower bound at which matches zinc blende structure, all other things being equal. upper extends way unity because relative CsCl are within 1% each above...
Patients with radioresistant breast cancers, including a large percentage of women triple negative cancer (TNBC), demonstrate limited response to radiation (RT) and increased locoregional recurrence; thus, strategies increase the efficacy RT in TNBC are critically needed. We that pan Bcl-2 family inhibition (ABT-263, rER: 1.52-1.56) or Bcl-xL specific (WEHI-539, A-1331852; 1.31-2.00) radiosensitized wild-type
Abstract Background: Clinical management of BC includes radiation therapy (RT), with most women receiving RT as part their treatment. Although effective, many develop locoregional recurrence, including a disproportionate number triple-negative or inflammatory BC. Unfortunately, the molecular mechanisms that underly response and intrinsic radioresistance are poorly understood. We hypothesized transcriptomic proteomic changes occur after ionizing in intrinsically radiosensitive resistant...
Abstract Purpose Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about interaction androgen (AR) estrogen (ER) in response to RT AR-positive, ER-positive (AR+/ER+) cancers. Here we assessed radiosensitisation AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation AR and/or ER. Methods Radiosensitisation was with antagonists (enzalutamide, apalutamide, darolutamide, seviteronel,...
Valinomycin is a well-known potassium-selective ion carrier, but the nature of its direct interaction with calcium ion, another biologically important cation, also considerable interest. We have determined first crystal structure valinomycin–calcium complex, which crystallises exclusively as 1:2 valinomycin:Ca2+ [VCa2(OTf)2(H2O)2]2+ in solid state (V = valinomycin, OTf triflate). Along solution phase 1:1 and 2:1 complexes been characterised acetonitrile by 1H NMR UV–Vis titration...
Abstract Purpose: Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC) local rates &lt;70% at 5 years these patients. Given the unsatisfactory outcomes, there clear need for intensification therapy, including radiation, Inhibition poly(adenosine diphosphate-ribose) polymerase 1 (PARP1), DNA repair protein, represents novel and promising strategy radiosensitizing aggressive tumors. The purpose this study was to investigate...
Abstract Background: Basal-like breast cancer (BC) has the highest rates of local recurrence despite use radiation therapy. Therefore, approaches for radiosensitization are critically needed patients with this subtype BC. Methods: Four independent datasets were used to correlate gene expression (LR) and Kaplan-Meier analysis validated impact TTK on LR. The METABRIC dataset was determine in BC subtypes. Clonogenic survival assays cell lines after inhibition (TTKi). Mouse models assess TTKi...
Abstract Purpose: Estrogen receptor (ER) expression is present in over 80% of breast tumors and has been shown to be a significant driver tumor initiation progression. Therefore, patients with ER-positive (ER+) cancers are given first-line therapies which target the ER downstream signaling. Ionizing radiation (RT) significantly improve locoregional control increase overall survival ER+ cancer. Similarly, endocrine therapy (ET) also metastasis-free women While both ET used cancer, effect on...
<p>Captions for Supplementary Figures 1-9</p>
<p>Supplementary Materials and Methods Section</p>