A5022441349- Renal cell carcinoma treatment
- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Gene Regulatory Network Analysis
- Mathematical Biology Tumor Growth
- Cancer Immunotherapy and Biomarkers
- Developmental Biology and Gene Regulation
- Theoretical and Computational Physics
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Advanced Mathematical Modeling in Engineering
- Advanced Fluorescence Microscopy Techniques
- Stochastic processes and statistical mechanics
- dental development and anomalies
- Diffusion Coefficients in Liquids
- Cellular Automata and Applications
- Congenital heart defects research
- Radiomics and Machine Learning in Medical Imaging
- Diffusion and Search Dynamics
- Advanced Biosensing Techniques and Applications
- Congenital limb and hand anomalies
- Cell Image Analysis Techniques
- Orthodontics and Dentofacial Orthopedics
- Craniofacial Disorders and Treatments
- Material Dynamics and Properties
AstraZeneca (Germany)
2021-2024
AstraZeneca (United States)
2022-2024
University of California, Irvine
2018-2020
Uppsala University
2015-2018
Highlights•Epidermal cells actively migrate into the interdigital mesenchyme•Active migration of epidermal is required for digit separation•Non-adhesive property periderm prevents epithelial fusion between digits•GRHL3 normal development and functionSummaryThe digits or toes, syndactyly, can be part complex syndromes, including van der Woude syndrome. A subset cases caused by dominant-negative mutations in transcription factor Grainyhead like-3 (GRHL3), Grhl3−/−mice have soft-tissue...
Abstract Purpose: MEDI0680 is a humanized anti–programmed cell death-1 (PD-1) antibody, and durvalumab an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity safety plus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal carcinoma who received at least one prior line antiangiogenic therapy. Patients Methods: either (20 mg/kg) (750 mg) or (240 mg),...
In computational systems biology, the mesoscopic model of reaction-diffusion kinetics is described by a continuous time, discrete space Markov process. To simulate diffusion stochastically, jump coefficients are obtained discretization equation. Using unstructured meshes to represent complicated geometries may lead negative when using piecewise linear finite elements. Several methods have been proposed modify enforce nonnegativity needed in stochastic setting. this paper, we present method...
Abstract Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 following concurrent chemoradiotherapy (cCRT) have shown clinical activity in locally advanced, unresectable NSCLC, e.g. with the PACIFIC regimen [1]. PD-L1 expression is typically assessed by pathologist scoring of immunohistochemically (IHC) stained tissue using tumor cell (TC) score. In this work, we present Quantitative Continuous Scoring (PD-L1 QCS) to digitally assess (Ventana SP263 assay), and analyze its...
Abstract Background: Volrustomig (MEDI5752) is designed to fully inhibit PD-1 while preferentially inhibiting CTLA-4 on activated PD-1+ T cells. In a FTiH trial, volrustomig demonstrated meaningful clinical activity in patients with solid tumors (including 1L RCC and NSCLC), acceptable safety profile, sustained receptor occupancy, cell proliferation at levels greater than seen clinically tolerable doses of inhibitors co-administration anti-PD(L)-1. We sought further characterize...
How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), Notch signaling, this system is highly robust. We combine NanoString experiments early D-V expression live imaging development zebrafish to construct computational model network....
Abstract Folate receptor alpha (FRα) is a cell surface GPI-anchored protein overexpressed in several solid tumors with highest prevalence ovarian cancer and lung adenocarcinoma but restricted expression normal tissues. An antibody drug conjugate (ADC) microtubule inhibitor (MTI) payload recently received accelerated approval from the FDA for FRα-expressing platinum-resistant cancer. We describe first time preclinical activity of AZD5335, an FRα-targeting conjugated to AZ’s proprietary...
We develop a mesoscopic modeling framework for diffusion in crowded environment, particularly targeting applications the of living cells. Through homogenization techniques we effectively coarse-grain detailed microscopic description into previously developed internal state diffusive framework. The observables model correspond to solutions macroscopic partial differential equations driven by stochastically varying fields space and time. Analytical numerical experiments illustrate
Mathematical models are important tools to study the excluded volume effects on reaction–diffusion systems, which known play an role inside living cells. Detailed microscopic simulations with off‐lattice Brownian dynamics become computationally expensive in crowded environments. In this study, authors therefore investigate extent on‐lattice approximations, so‐called cellular automata models, can be used simulate reactions and diffusion presence of crowding molecules. They show that is most...
<h3>Background</h3> The pathologist's visual assessment of tumor proportion score (TPS) with 25% cutoff on PD-L1 stained tissue samples is an established method to select metastatic NSCLC patients that are likely respond anti-PD-L1 monotherapy.<sup>1</sup> However, manual scoring often subject subjectivity in human perception<sup>2</sup> and there remains a critical need for more objective quantitative methods assess expression immuno-oncology. <h3>Methods</h3> We used deep learning (DL)...
Abstract Many targeted cancer therapies rely on biomarkers, which are assessed by standard pathologist scoring of immunohistochemically stained tissue. However, this process is subjective, semi-quantitative and does not assess expression heterogeneity. A quantitative method to measure IHC markers might therefore significantly improve patient selection particularly proteins expressed at low levels. To address these challenges, we have developed the Quantitative Continuous Scoring (QCS) that...
Mathematical models are important tools to study the excluded volume effects on reaction-diffusion systems, which known play an role inside living cells. Detailed microscopic simulations with off-lattice Brownian dynamics become computationally expensive in crowded environments. In this paper we therefore investigate extent on-lattice approximations, so called Cellular Automata models, can be used simulate reactions and diffusion presence of crowding molecules. We show that is most severely...
We present a multiscale approach to model diffusion in crowded environment and its effect on the reaction rates. Diffusion biological systems is often modeled by discrete space jump process order capture inherent noise of systems, which becomes important low copy number regime. To cell efficiently, we compute rates this mesoscopic from local first exit times, account for microscopic positions crowding molecules, while diffusing molecules coarser Cartesian grid. then extract macroscopic...
Supplementary Data from A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy Patients Advanced or Metastatic Clear-cell Renal Cell Carcinoma
Supplementary Figure from A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy Patients Advanced or Metastatic Clear-cell Renal Cell Carcinoma
Supplementary Data from A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy Patients Advanced or Metastatic Clear-cell Renal Cell Carcinoma
Supplementary Figure from A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy Patients Advanced or Metastatic Clear-cell Renal Cell Carcinoma
<div>AbstractPurpose:<p>MEDI0680 is a humanized anti–programmed cell death-1 (PD-1) antibody, and durvalumab an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity safety MEDI0680 plus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal carcinoma who received at least one prior line antiangiogenic therapy.</p>Patients...