A5071374889- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Melanoma and MAPK Pathways
- Immune cells in cancer
- Prostate Cancer Treatment and Research
- Mathematical Biology Tumor Growth
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- Prostate Cancer Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Cancer, Lipids, and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Alcoholism and Thiamine Deficiency
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Liver physiology and pathology
- Receptor Mechanisms and Signaling
- Metabolism and Genetic Disorders
- Neurological and metabolic disorders
- Biochemical Acid Research Studies
- Kruppel-like factors research
- Acute Myeloid Leukemia Research
University of New Mexico
2015-2025
New Mexico Cancer Center
2011-2023
University of Michigan
2007-2009
Dana-Farber Cancer Institute
1999-2003
Universitat de Barcelona
2003
Harvard University
1999-2002
Boston University
2001
Abstract Mutations in the androgen receptor (AR) that enable activation by antiandrogens occur hormone-refractory prostate cancer, suggesting mutant ARs are selected treatment. To validate this hypothesis, we compared AR variants metastases obtained rapid autopsy of patients treated with flutamide or bicalutamide, excision lymph node from hormone-naïve patients. mutations occurred at low levels all specimens, reflecting genetic heterogeneity cancer. Base changes recurring multiple samples...
Often considered to be a "dead" kinase, erbB3 is implicated in escape from erbB-targeted cancer therapies. Here, heregulin stimulation shown markedly upregulate kinase activity immunoprecipitates. Intact, activated phosphorylates tyrosine sites an exogenous peptide substrate, and this abolished by mutagenesis of lysine 723 the catalytic domain. Enhanced linked heterointeractions with catalytically active erbB2, since it largely blocked cells pretreated lapatinib or pertuzumab. erbB2...
Mutations within the epidermal growth factor receptor (EGFR/erbB1/Her1) are often associated with tumorigenesis. In particular, a number of EGFR mutants that demonstrate ligand-independent signaling common in non–small cell lung cancer (NSCLC), including kinase domain mutations L858R (also called L834R) and exon 19 deletions (e.g., ΔL747-P753insS), which collectively make up nearly 90% NSCLC. The molecular mechanisms by these confer constitutive activity remain unresolved. Using multiple...
Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian cells tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection fluorescent SKOV3.ip1 cells. Intra-vital microscopy mixed GFP-red protein (RFP) cell populations injected into peritoneum demonstrated that aggregate and attach as spheroids, emphasizing importance homotypic adhesion...
Ovarian cancer is the leading cause of death from gynecologic cancers in United States. Failure may be due to variable expression and/or complex interactions growth factor receptors individual tumors. As ErbB3-MET cooperativity implicated solid tumor resistance EGFR/ErbB2 inhibitors, we evaluated MET and all 4 ErbB family members ovarian cancers. Tissue arrays were prepared archival formalin-fixed paraffin-embedded samples, including 202 carcinomas (Stage I-IV) controls. Of patient only 25%...
Myeloproliferative neoplasms (MPNs) are often characterized by JAK2 or calreticulin (CALR) mutations, indicating aberrant trafficking in pathogenesis. This study focuses on Mpl and Jak2 association using two model systems: human erythroleukemia cells (HEL; JAK2V617F) K562 myeloid leukemia (JAK2WT). Consistent with a putative chaperone role for Jak2, associate both intracellular plasma membranes (shown proximity ligation assay) siRNA-mediated knockdown of led to trapping the endoplasmic...
Abstract Melanoma brain metastasis (MBM) is linked to dismal prognosis, low overall survival, and detected in up 80% of patients at autopsy. Circulating tumor cells (CTCs) are the smallest functional units cancer precursors fatal metastasis. We previously employed an unbiased multilevel approach discover a unique ribosomal protein large/small subunits (RPL/RPS) CTC gene signature associated with MBM. Here, we hypothesized that CTC-driven MBM secondary (“metastasis metastasis” per clinical...
<div>Abstract<p>Melanoma brain metastasis is linked to dismal prognosis and low overall survival detected in up 80% of patients at autopsy. Circulating tumor cells (CTC) are the smallest functional units cancer precursors fatal metastasis. We previously used an unbiased multilevel approach discover a unique ribosomal protein large/small subunit (RPL/RPS) CTC gene signature associated with melanoma In this study, we hypothesized that CTC-driven secondary (“metastasis metastasis”...
<p>Capture and interrogation of CTCs from huNBSGW NBSGW CDXs by the FDA-approved CTC Parsortix platform. Blood second-generation was collected at end study immunostained for visualization single (MelA<sup>+</sup>/DAPI<sup>+</sup>/CD45<sup>−</sup> cells; <b>A</b>) clusters (<b>B</b>). <b>C,</b> Cells healthy donor blood (MelA<sup>–</sup>/DAPI<sup>+</sup>/CD45<sup>+</sup>) were...
<p>Heat maps of humanized vs non-humanized brain tissues</p>
<p>Table S3</p>
<p>Metastatic patterns of first-generation CDX mice by IVIS imaging. Gender-specific huNBSGW (<b>A</b>) and immunodeficient NBSGW (<b>B</b>) were engrafted with CTC-derived clonal cells intracardiac injection (70W-SM3-Luc2; 5.0 × 10E5/animal). imaging was performed every week to evaluate metastatic onset. The last time point (5 weeks) is shown. Mice MBM are circled. Following necropsy, pathologic evaluation revealed multifocal in (<b>C</b>)...
<p>Spatial single-cell gene expression analysis of CTC-derived cell:B-cell interactions employing 10x Genomics Xenium platform (<a href="http://www.10xgenomics.com/" target="_blank">www.10xgenomics.com</a>). HuNBSGW A2.1 mice were engrafted with clonal cells via intracardiac injection (70W-SM3-Luc2; 5.0 × 10<sup>5</sup> cells/animal). <b>A,</b> Dim plot shows 2D scatter representing cell clusters in reduced space. Cell annotations are shown on the...
<p>Detection and quantitation of CTC (MelA<sup>+</sup>/DAPI<sup>+</sup>/CD45<sup>−</sup>):B-cell (CD19<sup>+</sup>/DAPI<sup>+</sup>/CD45<sup>+</sup>) clusters in blood patients with melanoma by Parsortix. Visualization CTC:B-cell primary (<b>A</b>), metastatic (<b>B</b>) melanoma, single B cells (<b>C</b>) patient samples...
<p>Bar plots analyses of 10x Xenium clusters</p>
<p>The melanoma brain–liver metastasis axis. <b>A</b> and <b>B,</b> MBM-generated liver MBM of second-generation mice. MBM/liver (yellow arrows) from huNBSGW (<b>A</b>) NBSGW (<b>B</b>) mice engrafted via intracardiac injection with first-generation CDX cells (5.0 × 10E5 cells/animal). Quantification shows higher %, number, size in (bottom). <b>C,</b> Statistical significance (***, <i>P</i> value < 0.001) for...
<p>Flowchart of experimental strategy</p>
<p>Table S2</p>
<p>IVIS quantification of the1st generation CDXs</p>
<p>Heat maps of humanized vs non-humanized intestine tissues</p>
<p>Table S4</p>
<p>Xenium analyses of HuNBSGW intestine</p>
<p>IVIS determination to metastasis distant organs</p>