A5021203811- Melanoma and MAPK Pathways
- Enzyme function and inhibition
- Hepatocellular Carcinoma Treatment and Prognosis
- PI3K/AKT/mTOR signaling in cancer
- Lymphatic System and Diseases
- Radiomics and Machine Learning in Medical Imaging
- Quinazolinone synthesis and applications
- Cancer Genomics and Diagnostics
- Synthesis and Catalytic Reactions
- Electrochemical sensors and biosensors
- Cancer Mechanisms and Therapy
- Cutaneous Melanoma Detection and Management
- Molecular Biology Techniques and Applications
- Cell Adhesion Molecules Research
- Liver Disease Diagnosis and Treatment
- Mass Spectrometry Techniques and Applications
- Medical Image Segmentation Techniques
- Genetics, Aging, and Longevity in Model Organisms
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Cellular Mechanics and Interactions
- Cholinesterase and Neurodegenerative Diseases
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Amino Acid Enzymes and Metabolism
The University of Texas MD Anderson Cancer Center
2004-2024
Centre for Cancer Biology
2023
AC Camargo Hospital
2018
National Institutes of Health
2015
Lovelace Respiratory Research Institute
2009
New Mexico State University
2004
Duke Medical Center
1991-1997
Duke University Hospital
1996-1997
University of Pennsylvania
1991
Recently, a rare activating mutation of AKT1 (E17K) has been reported in breast, ovarian, and colorectal cancers. However, analogous mutations AKT2 or AKT3 have not identified any cancer lineage. To determine the prevalence AKT E17K melanoma, most aggressive form skin cancer, we analysed 137 human melanoma specimens 65 cell lines for previously described AKT1, AKT3. We single mutation. Remarkably, unidentified was detected two melanomas (from one patient) as well lines. The results...
PURPOSE: Activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway has been implicated in melanoma based primarily on prevalence mutations PTEN and NRAS. To improve our understanding regulation clinical significance PI3K-AKT melanoma, we quantitatively measured levels phosphorylated AKT, its substrate GSK3alpha/beta, negative regulator metastases. Results were compared with mutational status, outcomes, sites metastasis. EXPERIMENTAL DESIGN: DNA protein isolated from dissected frozen...
Eleven amino acid substitutions at Val-12 1 of human carbonic anhydrase I1 including Gly, Ala, Ser, Leu, Ile, Lys, and Arg, were constructed by site-directed mutagenesis.This residue is the mouth hydrophobic pocket in enzyme active site.The COz hydrase activity p-nitrophenyl esterase these CAII variants correlate with hydrophobicity residue, suggesting that character this important for catalysis.The effects mutations on steady-state kinetics hydration occur mainly kCatlK, K,, consistent...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFunctional consequences of engineering the hydrophobic pocket carbonic anhydrase IICarol A. Fierke, Tiffany L. Calderone, and Joseph F. KrebsCite this: Biochemistry 1991, 30, 46, 11054–11063Publication Date (Print):November 19, 1991Publication History Published online1 May 2002Published inissue 19 November 1991https://pubs.acs.org/doi/10.1021/bi00110a007https://doi.org/10.1021/bi00110a007research-articleACS PublicationsRequest reuse...
Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding this complication, we performed immune profiling on post-mortem tissue from patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis heart demonstrated findings consistent giant cell (GCM). The infiltrate in was largely comprised CD4+ T cells,...
Telomerase reverse transcriptase (TERT) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated these mutations. We retrieved data on C228T C250T promoter 196 HCCs from The Cancer Genome Atlas. measured plasma cfDNA 218 81 without imaging evidence HCC. prevalence Atlas specimens...
Background & AimsThe effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance the screening modalities.MethodsWe developed a multicenter prospective cohort cirrhotic undergoing MRI, applied global untargeted metabolomics 612 longitudinal serum samples from 203 patients. Among them, 37 HCC during follow-up.ResultsWe identified 150 metabolites significant abundance changes collected...
Uniform double labeling of proteins for NMR studies can be prohibitively expensive, even with an efficient expression and purification scheme, due largely to the high cost [13C6, 99%]glucose. We demonstrate here that uniformly (greater than 95%) 13C 15N double-labeled prepared structure/function by growing cells in defined media containing sodium [1,2-13C2, 99%]acetate as sole carbon source [15N, 99%]ammonium chloride nitrogen source. In addition, we this scheme extended include uniform...
The bioactive phospholipid lysophosphatidic acid (LPA) and its receptors LPA1-3 are aberrantly expressed in many types of human cancer. LPA has been reported to induce tumor cell proliferation, migration, cytokine production. However, whether exerts an effect on lymphatic endothelial cells (LECs) or lymphangiogenesis, a process new vessel formation that is associated with increased metastasis poor prognosis cancer patients, unknown. Here, we show induces survival, tube formation, promotes...
Initiatives such as The Cancer Genome Atlas (TCGA) and International Consortium (ICGC) have generated high-quality, multi-platform molecular data from thousands of frozen tumor samples. While these initiatives provided invaluable insight into cancer biology, a tremendous potential resource remains largely untapped in formalin-fixed, paraffin-embedded (FFPE) samples that are more readily available, but which can present technical challenges due to crosslinking fragile molecules RNA.We...
Significance Formation of metastasis is the most deadly step in melanoma progression and primarily occurs through lymphatic vasculature. Unfortunately, little known regarding underlying molecular mechanisms that enable interactions between cells vessels. In this study, we developed an unbiased approach using combinatorial peptide libraries displayed on phage coat proteins to identify cell–cell interacting at vessel–tumor cell interface. Successful application led identification surface...
Abstract Image segmentation of the liver is an important step in treatment planning for cancer. However, manual at a large scale not practical, leading to increasing reliance on deep learning models automatically segment liver. This manuscript develops generalizable model T1-weighted MR images. In particular, three distinct architectures (nnUNet, PocketNet, Swin UNETR) were considered using data gathered from six geographically different institutions. A total 819 images both public and...
Image segmentation of the liver is an important step in several treatments for cancer. However, manual at a large scale not practical, leading to increasing reliance on deep learning models automatically segment liver. This manuscript develops model T1w MR images. We sought determine best architecture by training, validating, and testing three different architectures using total 819 images gathered from six datasets, both publicly internally available. Our experiments compared each...
Clinically deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these tend perform well in most instances, which could exacerbate automation bias. Therefore, detecting out-of-distribution images at inference is critical warn that model likely failed. This work applied Mahalanobis distance (MD) post hoc bottleneck features four Swin UNETR and nnU-net segmented liver T1-weighted magnetic...
9022 Background: Activating mutations of BRAF are highly prevalent in melanoma. However, multiple lines evidence suggest that other pathways must also contribute to this disease. Activation the PI3K-AKT pathway has been implicated melanoma by NRAS and PTEN. Little direct information is known about activation signaling melanoma, particularly metastases. Methods: Proteins isolated from 99 frozen tumors were measured reverse phase protein arrays (RRPA). A total 53 proteins assessed using...
e20002 Background: The increasing availability of molecular profiling techniques amenable to FFPE tissue presents a key opportunity study the basis melanoma. In order optimize our methodological approaches for melanoma specimens planned integrative analyses, we compared various DNA and RNA analyte extraction melanin removal methods on yield, quality, profiles. Methods: Primary (n = 2) metastatic 6) with varying degrees pigmentation (3-none/minimal, 3-moderate, 2-high) were used systematic...
Supplementary Data from Integrated Molecular and Clinical Analysis of AKT Activation in Metastatic Melanoma
<div>Abstract<p><b>Purpose:</b> Activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway has been implicated in melanoma based primarily on prevalence mutations PTEN and NRAS. To improve our understanding regulation clinical significance PI3K-AKT melanoma, we quantitatively measured levels phosphorylated AKT, its substrate GSK3α/β, negative regulator metastases. Results were compared with mutational status, outcomes, sites...
<div>Abstract<p><b>Purpose:</b> Activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway has been implicated in melanoma based primarily on prevalence mutations PTEN and NRAS. To improve our understanding regulation clinical significance PI3K-AKT melanoma, we quantitatively measured levels phosphorylated AKT, its substrate GSK3α/β, negative regulator metastases. Results were compared with mutational status, outcomes, sites...