A5004015323- Ocular Oncology and Treatments
- Retinal Development and Disorders
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Radiomics and Machine Learning in Medical Imaging
- Histone Deacetylase Inhibitors Research
- Chromatin Remodeling and Cancer
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Melanoma and MAPK Pathways
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- melanin and skin pigmentation
- Medical Imaging Techniques and Applications
- RNA modifications and cancer
- Advanced X-ray and CT Imaging
- Cutaneous Melanoma Detection and Management
- AI in cancer detection
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
- MRI in cancer diagnosis
- bioluminescence and chemiluminescence research
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- Lung Cancer Treatments and Mutations
Washington University in St. Louis
2014-2024
University of Washington
2024
John Cochran VA Medical Center
2014
Pediatrics and Genetics
2014
Oldenburger Institut für Informatik
2007-2012
Molecular Oncology (United States)
2008
Institute of Molecular Biology and Biophysics
1990-2005
An Eye on Metastasis Despite the considerable progress being made in elucidating cell biology of metastasis, little is known about genetic alterations that promote metastasis human tumors, cause most cancer deaths. A potentially important clue now emerges from work Harbour et al. (p. 1410 , published online 4 November), who used an exome-sequencing approach to search for mutations uveal melanomas, eye associated with a high rate fatal metastasis. Remarkably, over 80% tumor samples metastatic...
Abstract Melanomas are notoriously difficult to classify because of a lack discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes discriminate class 1 (low-grade) from 2 (high-grade) include highly significant clusters down-regulated genes chromosome 3 up-regulated 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size...
Early/initiating oncogenic mutations have been identified for many cancers, but such remain unidentified in uveal melanoma (UM). An extensive search was undertaken, focusing on the RAF/MEK/ERK pathway, which is often target of initiating other types cancer.DNA samples from primary UMs were analyzed 24 potential oncogenes that affect pathway. For GNAQ, a stimulatory alpha(q) G-protein subunit recently found to be mutated UMs, resequencing expanded include 67 and 22 peripheral blood samples....
Metastasis is responsible for the death of most cancer patients, yet few therapeutic agents are available which specifically target molecular events that lead to metastasis. We recently showed inactivating mutations in tumor suppressor gene BAP1 closely associated with loss melanocytic differentiation uveal melanoma (UM) and The purpose this study was identify reverse phenotypic effects UM.In silico screens were done compounds predicted differentiate UM cells using Gene Set Enrichment...
The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting passage of molecules and microorganisms. Despite this barrier, however, fungal pathogen Cryptococcus neoformans invades brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in lung, experimental evidence suggests host phagocytes play role subsequent dissemination, although remains ill defined. Additionally, disparate approaches have been...
Abstract Microarray gene expression profiling is a powerful tool for generating molecular cancer classifications. However, elucidating biological insights from these large data sets has been challenging. Previously, we identified expression-based classification of primary uveal melanomas that accurately predicts metastatic death. Class 1 tumors have low risk and class 2 high Here, used genes discriminate tumor classes to identify correlates the aggressive signature. A search Gene Ontology...
Abstract Purpose: To compare a gene expression–based classifier versus the standard genetic prognostic marker, monosomy 3, for predicting metastasis in uveal melanoma. Experimental Design: Gene expression profiling, fluorescence situ hybridization (FISH), and array comparative genomic (aCGH) were done on 67 primary melanomas. Clinical pathologic factors also assessed. Variables analyzed by Cox proportional hazards, Kaplan-Meier analysis, sensitivity, specificity, positive negative predictive...
Uveal (ocular) melanoma is a highly aggressive cancer that leads to metastatic death in up half of patients despite successful local therapy. Biomarkers risk are critically needed institute new adjuvant treatment strategies high-risk patients. Previously, we showed two prognostically significant molecular subtypes uveal could be identified based on gene expression profiling the primary tumor. In this study, investigated value micro-RNA (miRNA) patterns predicting risk. A genome-wide,...
Abstract Background Uveal melanoma is a highly aggressive cancer with strong propensity for metastasis, yet little known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit class 2 gene expression profile, contain inactivating mutations in tumor suppressor BAP1 . The aim of study was to investigate role progression. Methods cells were studied following RNAi-mediated depletion using proliferation, BrdU...
Abstract Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison carcinogen-induced murine and human OSCCs with indolent or metastatic yielded results surprising translational relevance. Experimental Design: Murine OSCC lines were subjected to next-generation sequencing (NGS) define their mutational landscape, novel candidate cancer genes, assess for...
A plant-derived compound may treat patients with diseases caused by Gα mutations.
Abstract Purpose: The molecular pathogenesis of uveal melanoma is poorly understood but usually accompanied by amplification chromosome 8q, suggesting the activation one or more oncogenes. We recently identified a gene expression profile that distinguishes low-grade from high-grade melanomas. In this profile, cluster genes at 8q was overexpressed in tumors, providing an opportunity to search for potential oncogenes region. Experimental Design: Gene microarray analysis done on 25 primary...
Abstract Purpose: Aneuploidy is a hallmark of cancer and closely linked to metastasis poor clinical outcome. Yet, the mechanisms leading aneuploidy its role in tumor progression remain poorly understood. The extensive complex karyotypic abnormalities seen many solid tumors could hinder identification pathogenetically relevant chromosomal alterations. Uveal melanoma an attractive for studying because it relatively homogeneous that highly metastatic has low nonspecific instability....
Abstract Purpose: Loss of chromosome 3 is strongly associated with metastasis in uveal melanoma and has been proposed as the basis for clinical prognostic testing. It not known whether techniques that identify loss heterozygosity predict more accurately than those detect only numerical (monosomy 3). Experimental Design: Fifty-three melanomas were analyzed by 28 single nucleotide polymorphisms (SNP) across 3. SNP was compared fluorescence situ hybridization (FISH) array-based comparative...
Uveal melanomas frequently metastasize and cause patient death. Many clinical, histopathologic, molecular, genetic factors have been linked to metastasis. We hypothesized that understanding the relationships between, relative prognostic significance of these would provide new insights into pathogenesis To this end, we collected pathologic, molecular data for 65 uveal melanomas, including age, sex, tumor size, location, cell type, vasculogenic mimicry looping matrix patterns, gene expression...
Abstract Purpose: To identify genes that modify metastatic risk in uveal melanoma, a type of cancer is valuable for studying metastasis because its remarkably consistent pattern and well-characterized gene expression signature associated with metastasis. Experimental Design: We analyzed 53 primary melanomas by profiling, array-based comparative genomic hybridization, global DNA methylation single nucleotide polymorphism–based detection loss heterozygosity to modifiers risk. A candidate gene,...
Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such relies heavily on image post-processing tools automated quantitation. Their deployment in the context research necessitates interoperability with systems. Comparison established outcomes and evaluation tasks motivate integration imaging data, use standardized approaches to support annotation sharing analysis results semantics. We developed methodology these Positron...
Interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1) is classically important for immune function. However, we found recently that these receptors have a second role, in embryogenesis, where they mediate cell-cell interactions are skeletal muscle differentiation. Here, present evidence an expanding role murine development. and VCAM-1 were at embryonic sites hematopoiesis, suggesting during embryogenesis parallels their hematopoietic function adult bone marrow. During...
Abstract Purpose: Mutational activation of GNAQ or GNA11 (GNAQ/11), detected in >90% uveal melanomas, leads to constitutive oncogenic pathways, including MAPK and YAP. To date, chemo- pathway-targeted therapies, either alone combination, have proven ineffective the treatment patients with metastatic melanoma. Experimental Design: We tested efficacy chloroquine hydroxychloroquine, combination pathway inhibition GNAQ/11-mutated cells vitro vivo identified mechanisms MEK1/2 inhibitor...
Uveal melanoma (UM) is the most common intraocular tumor in adults. Nearly half of UM patients develop metastatic disease and often succumb within months because effective therapy lacking. A novel therapeutic approach has been suggested by discovery that cell lines driven mutant constitutively active Gq or G11 can be targeted FR900359 (FR) YM-254890, which are bioavailable, selective inhibitors Gq/11/14 subfamily heterotrimeric G proteins. Here, we have addressed potential FR for UM. We...