A5013641806- Hedgehog Signaling Pathway Studies
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Developmental Biology and Gene Regulation
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Microbial Inactivation Methods
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Medical Imaging Techniques and Applications
- Pediatric health and respiratory diseases
- Cell Image Analysis Techniques
- Advanced MRI Techniques and Applications
- Cancer Treatment and Pharmacology
- Respiratory and Cough-Related Research
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Brain Metastases and Treatment
- Cancer-related Molecular Pathways
Presage Biosciences (United States)
2013-2022
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2010-2013
Fred Hutch Cancer Center
2004-2012
Cellular Research (United States)
2008
University of Washington
2006
Abstract To develop a genetically faithful model of medulloblastoma with increased tumor incidence compared the current best we activated Sonic Hedgehog (Shh) pathway by transgenically expressing constitutively active form Smoothened in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This resulted early cell hyper-proliferation and 48% formation. Gene expression studies showed an increase known Shh targets Gli1 Nmyc that correlated increasing hyperplasia Notch2 Notch target...
Abstract Toward the goal of generating a mouse medulloblastoma model with increased tumor incidence, we developed homozygous version our ND2:SmoA1 model. Medulloblastomas form in 94% Smo/Smo mice by 2 months age. Tumor formation is, thus, predictable age, before symptomatic appearance larger lesions. This high incidence and early onset tumors is ideal for preclinical studies because can be enrolled symptom greater latency period late-stage disease. also display leptomeningeal dissemination...
The Sonic Hedgehog (Shh) pathway drives a subset of medulloblastomas, malignant neuroectodermal brain cancer, and other cancers. Small-molecule Shh inhibitors have induced tumor regression in mice patients with medulloblastoma; however, drug resistance rapidly emerges, some cases via de novo mutation the target. Here we assess response mechanisms to natural product derivative saridegib an aggressive Shh-driven mouse medulloblastoma model. In this model, treatment reduction significantly...
Simultaneous in vivo assessment of multiple cancer drugs and drug combinations using microinjection technology predicts systemic response model tumors has shown feasibility for efficacy a pilot study patients.
TAK-981, a first-in-class small-molecule SUMOylation inhibitor, activates type I interferon signaling to promote antitumor immune responses in mice.
Abstract We examined the genetic requirements for Myc family of oncogenes in normal Sonic hedgehog (Shh)–mediated cerebellar granule neuronal precursor (GNP) expansion and Shh pathway–induced medulloblastoma formation. In GNP-enriched cultures derived from N-mycFl/Fl c-mycFl/Fl mice, disruption N-myc, but not c-myc, inhibited proliferative response to Shh. Conditional deletion c-myc revealed that, although it is necessary general regulation brain growth, less important development GNP than...
ABSTRACT Background and Methods Surgery remains the standard of care for non‐small cell lung cancer (NSCLC) but is applicable to ≤ 30% patients. Pulsed Electric Fields (PEF) ablation uses short‐duration, high‐voltage electrical pulses induce death without relying on thermal mechanisms. Safety findings are reported from a two‐arm, non‐randomized, study evaluating use PEF in patients with early‐stage NSCLC. energy was delivered bronchoscopically or percutaneously 36 suspected confirmed NSCLC...
Deregulated developmental processes in the cerebellum cause medulloblastoma, most common pediatric brain malignancy. About 25 to 30% of cases are caused by mutations increasing activity Sonic hedgehog (Shh) pathway, a critical mitogen cerebellar development. The proto-oncogene Smoothened (Smo) is key transducer Shh pathway. Activating Smo that lead constitutive pathway have been identified human medulloblastoma. To understand and oncogenic effects two closely positioned point Smo, we...
<h3>Background</h3> Enhancing anti-tumor immunity is a foundational therapeutic strategy against cancer.<sup>1</sup> The Aliya Pulsed Electric Fields (PEF) proprietary system has been shown to promote local and systemic immune activation in pre-clinical murine models through the of immunogenic cell death (ICD) release damage associated molecular patterns (DAMPs) tumor-specific antigens.<sup>2 3</sup> Unlike apoptosis, often immunosuppressive, ICD mechanisms generate potent response by...
<h3>Background</h3> Tertiary lymphoid structures (TLS) may develop in non-lymphoid tissues response to a variety of different stimuli and can serve as foci for generating anti-tumor immunity.<sup>1</sup> TLS formation is emerging strong prognostic predictive biomarker<sup>2</sup> associated with patient survival benefits NSCLC.<sup>3,4</sup>Pulsed Electric Fields (PEF) have been reported induce an immunogenic form cell death thus enhance adaptive immunity the setting cancer. The...
Abstract Purpose/Objectives: The human tumor microenvironment (TME) has a dramatic impact on cancer prognosis and therapeutic response, but accurate models of the native TME do not exist. Comparative In Vivo Oncology (CIVO) platform was developed as means to assess effect investigational agents in Phase 0 microdosing study. CIVO clinically validated using approved is used for first time here an agent - SUMOylation inhibitor TAK-981 HNSCC. Materials/Methods: Eligible subjects have confirmed...
Abstract The complex interplay between a drug, the tumor and surrounding microenvironment is critical determinant in how patient will respond to their selected cancer therapy. Yet date, this response has been difficult evaluate prior late stage clinical investigation. To enable means for testing investigational agents earlier development process but still directly human patients, way that limits risk of adverse effects provides an indication efficacy, Presage Biosciences developed technology...
Abstract Background The cyclin-dependent kinase inhibitor p27 Kip1 functions during normal cerebellar development and has demonstrated tumor suppressor in mouse models of medulloblastoma. Because P27 loss is associated with increased proliferation, we assessed whether absence surgical medulloblastoma specimens correlated response to therapy pediatric patients enrolled two large studies. Additionally, examined the functional consequence SmoA1 model distinguish reduces initiation or slows...
Abstract Purpose/Objectives: Individual tumor complexity and the emergence of treatment resistance mechanisms have proven challenging for oncology drug development, methods prioritizing combination therapy approaches are needed. The CIVO (Comparative In Vivo Oncology) platform can simultaneously deliver up to 8 drugs combinations in microdose amounts distinct, trackable regions within a single intact tumor, enabling studies that assess multiple directly patients during early development....
Purpose To facilitate decision making in the oncology clinic, technologies have recently been developed to independently inject and assess multiple anticancer agents directly a patient's tumor. increase flexibility of this approach beyond histological readouts response, contrast‐enhanced MRI was evaluated for detection cell death living tumors after injection. Methods A six‐needle arrayed microinjection device designed provide head‐to‐head comparisons chemotherapy responses used. Xenografted...
Abstract Proper selection of anti-cancer agents at the earliest stage patient treatment following diagnosis disease relapse is expected to substantially impact clinical response treatment. Currently, genomic approaches personalized cancer treatments have been yielded mixed results, while empirical tests assess tumor responsiveness limited ex vivo systems that disrupt native microenvironment and show predictive value. To address need for multiplexed in chemosensitivity testing, we developed a...
Abstract Assessment of anti-cancer drug efficacy is an imprecise and challenging undertaking. Early candidate selection typically based on results from systemically treated animal models later by performance in human trials where patients are exposed to often toxic levels drug, prior obtaining readouts tumor response. In both these testing models, only one can be tested at a time. Using methods, over 90% new oncology drugs fail provide benefit for clinical trials. To improve the predictive...
<div>Abstract<p>To develop a genetically faithful model of medulloblastoma with increased tumor incidence compared the current best we activated Sonic Hedgehog (Shh) pathway by transgenically expressing constitutively active form <i>Smoothened</i> in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This resulted early cell hyper-proliferation and 48% formation. Gene expression studies showed an increase known Shh targets <i>Gli1</i>...
<div>Abstract<p>To develop a genetically faithful model of medulloblastoma with increased tumor incidence compared the current best we activated Sonic Hedgehog (Shh) pathway by transgenically expressing constitutively active form <i>Smoothened</i> in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This resulted early cell hyper-proliferation and 48% formation. Gene expression studies showed an increase known Shh targets <i>Gli1</i>...
3 Tables & 2 Figures from The SmoA1 Mouse Model Reveals That Notch Signaling Is Critical for the Growth and Survival of Sonic Hedgehog-Induced Medulloblastomas
3 Tables & 2 Figures from The SmoA1 Mouse Model Reveals That Notch Signaling Is Critical for the Growth and Survival of Sonic Hedgehog-Induced Medulloblastomas
Supplementary Figure 2 from The Smo/Smo Model: Hedgehog-Induced Medulloblastoma with 90% Incidence and Leptomeningeal Spread