A5045649474- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Trace Elements in Health
- Cell Adhesion Molecules Research
- Ferrocene Chemistry and Applications
- Radiopharmaceutical Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Cell death mechanisms and regulation
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Neuroscience and Neuropharmacology Research
- Immunotherapy and Immune Responses
- Caveolin-1 and cellular processes
- Lymphoma Diagnosis and Treatment
- Nanoparticle-Based Drug Delivery
- Medicinal Plant Pharmacodynamics Research
- Urinary and Genital Oncology Studies
- Cancer Research and Treatments
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Ion channel regulation and function
- Multiple Myeloma Research and Treatments
- Bladder and Urothelial Cancer Treatments
- Chemokine receptors and signaling
Seagen (United States)
2009-2023
Seagen (Canada)
2009
University of Colorado Anschutz Medical Campus
2000-2003
University of Colorado Health
2001-2003
Veterans Health Administration
2000-2003
Merck & Co., Inc., Rahway, NJ, USA (United States)
2001
In our previous study we showed that insulin-like growth factor-I induces a cAMP-response element (CRE) site-containing Bcl-2 promoter through novel signaling pathway involving mitogen-activated protein kinase 6/p38β kinase/MAP kinase-activated kinase-3/cAMP-response element-binding (CREB) (Pugazhenthi, S., Miller, E., Sable, C., Young, P., Heidenreich, K. A., Boxer, L. M., and Reusch, J. E.-B. (1999)J. Biol. Chem. 274, 27529–27535). the present investigation, define second contributing to...
CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed >or=50% of pancreatic, gastric intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that panel established hepatocellular, pancreatic cancer cell lines at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human antibody (AC133) conjugated potent...
Insulin is a potent adipogenic hormone that triggers an induction of series transcription factors governing differentiation pre-adipocytes into mature adipocytes. However, the exact link between insulin signaling cascade and intrinsic adipogenesis remains incompletely understood. Herein we demonstrate inhibition prenylation p21ras Rho-A arrests insulin-stimulated adipogenesis. Inhibition farnesylation also blocked ability to activate mitogen-activated protein (MAP) kinase cyclic AMP response...
In this article, we describe a novel antibody-drug conjugate (ADC; SGN-LIV1A), targeting the zinc transporter LIV-1 (SLC39A6) for treatment of metastatic breast cancer. was previously known to be expressed by estrogen receptor-positive cancers. study, show that expression is maintained after hormonal therapy in primary and sites also upregulated triple-negative addition cancer, other indications showing include melanoma, prostate, ovarian, uterine SGN-LIV1A consists humanized antibody...
We hypothesized that cAMP response element-binding protein (CREB) could function as a molecular determinant of smooth muscle cell fate. In arterial sections from the systemic and pulmonary circulation, CREB content was high in proliferation-resistant medial subpopulations cells low proliferation-prone regions. vessels neonatal calves exposed to chronic hypoxia, depleted (SMC) proliferation accelerated. Induction quiescence by serum deprivation culture led increased content. Highly...
Abstract Generation of oxidative stress/reactive oxygen species (ROS) is one the causes neuronal apoptosis. We have examined effects ROS at transcriptional level in an immortalized hippocampal cell line (H19‐7) and rat primary neurons. Treatment H19‐7 cells with hydrogen peroxide (150 µ m ) resulted a 40% decrease Bcl‐2 protein parallel bcl‐2 mRNA levels. overexpressing were found to be resistant ROS‐induced had previously shown that promoter activity positively regulated by transcription...
Voltage-dependent calcium channels (VDCCs) are multimeric complexes composed of a pore-forming α 1 subunit together with several accessory subunits, including 2 δ, β, and, in some cases, γ subunits. A family VDCCs known as the L-type formed specifically from 1S (skeletal muscle), 1C (in heart and brain), 1D (mainly brain, heart, endocrine tissue), 1F (retina). Neuroendocrine currents have significant role control neurosecretion can be inhibited by GTP-binding (G-) proteins. However,...
Abstract Identifying factors that determine the sensitivity or resistance of cancer cells to cytotoxicity by antibody-drug conjugates is essential in development such for therapy. Here monoclonal antibody L49 used target melanotransferrin, a glycosylphosphatidylinositol-anchored glycoprotein first identified as p97, cell-surface marker melanomas. was conjugated via proteolytically cleavable valine-citrulline linker antimitotic drug, monomethylauristatin F (vcMMAF). Effective drug release...
CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas highly restricted normal tissues. The profiling has been limited the lack a CD70-specific reagent that works formalin-fixed paraffin-embedded (FFPE) We generated murine monoclonal antibodies (mAbs) specific validated their specificity by western blot analysis developed protocol immunohistochemistry on FFPE CD70+ tumour cell lines were used testing...
SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. consists of humanized antibody, hL49, with high specificity and affinity for CD228 that stably conjugated 8 molecules the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data...
We hypothesized that diabetes and glucose-induced reactive oxygen species lead to depletion of cAMP response element-binding protein (CREB) content in the vasculature. In primary cultures smooth muscle cells (SMC) high medium glucose decreased CREB function but increased SMC chemokinesis entry into cell cycle. These effects were blocked by pretreatment with antioxidants. High intracellular detected CM-H<sub>2</sub>DCFA. exposed oxidative stress (H<sub>2</sub>O<sub>2</sub>) demonstrated a...
Cytokines are known to induce apoptosis of pancreatic β-cells. Impaired expression the anti-apoptotic gene bcl-2 is one mechanisms involved. In this study, we identified a defect involving transcription factor cAMP-response element-binding protein (CREB) in bcl-2. Exposure mouse β-cell line, MIN6 cells, cytokines (interleukin-1β, tumor necrosis factor-α, and interferon-γ) led significant (p < 0.01) decrease Bcl-2 mRNA levels. decreased (56%) activity promoter that contains element (CRE)...
Despite therapeutic advances, the long-term survival rates for acute myeloid leukemia (AML) are estimated to be 10% or less, pointing need better treatment options. AML cells express marker CD33, making it amenable CD33-targeted therapy. Thus, in vitro and vivo anti-tumor activities of lintuzumab (SGN-33), a humanized monoclonal anti-CD33 antibody undergoing clinical evaluation, were investigated. In assays used assess ability mediate effector functions decrease production growth factors...
Abstract The antibody-drug conjugate enfortumab vedotin (EV; AGS22C3E) targets Nectin-4 expressing tumor cells by delivering MMAE, a potent microtubule disrupting agent, to induce cell death. EV has demonstrated single agent activity and encouraging (71% ORR) when combined with pembrolizumab (anti-PD-1) in the 1L setting of cis-ineligible metastatic urothelial carcinoma (mUC) (EV-103, NCT03288545). Here we that may promote multiple mechanisms action including bystander killing hallmarks...
Abstract Multiple myeloma (MM) is a hematologic malignancy of transformed plasma cells. In spite recent advances, MM remains an incurable disease, underscoring the need to develop new targeted biological therapeutics augment existing treatments. this study we describe SGN-CD352A, potent CD352-targeting antibody-drug conjugate (ADC) under development for treatment MM. CD352, or SLAMF6 (Signaling Lymphocyte Activation Molecule family member 6), type 1 membrane protein in SLAM immunoreceptors....
<h3>Background</h3> Enfortumab vedotin (EV) is a first-in-class Nectin-4-directed antibody-drug conjugate (ADC) with demonstrated improved overall survival in patients previously treated advanced-stage urothelial carcinoma.<sup>1</sup> EV comprised of fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) by protease cleavable maleimidocaproyl-valine-citrulline linker. has multifaceted mechanism action. Previously, we that induces...
Abstract CD70 is a member of the tumor necrosis factor superfamily that aberrantly expressed in several solid tumors and hematologic malignancies, including clear cell papillary renal carcinoma (RCC) non-Hodgkin lymphoma (NHL). Normal expression limited to stromal cells thymic medulla, mature dendritic cells, activated B T lymphocytes. Thus, an attractive target for antibody-drug conjugate (ADC) based therapy. Using panel positive RCC lines xenograft models, we have previously demonstrated...
Experiments in vascular smooth muscle cells (SMCs) indicate that the transcription factor cAMP response element-binding protein (CREB), cyclic nucleotide protein, suppresses expression of platelet-derived growth factor-α receptor gene (PDGFRα). Adenovirus-mediated constitutively active CREB mutants decreases PDGFRα mRNA, and promoter-luciferase reporter activity cultured SMCs. Expression dominant negative A-CREB, increases content PDGFRα-promoter Active prevents activation by...
Abstract LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified an estrogen-inducible gene in breast cancer derived cell lines. downstream target STAT3, promotes epithelial to mesenchymal transition that important malignant progression metastasis. Consistent with its role cancer, we determined by immunohistochemical (IHC) analysis LIV-1 expressed subtypes metastatic cancers (ER+/HER2-, HER2+ triple negative). In healthy human tissues,...
TPS1143 Background: First identified as an estrogen-inducible gene in a breast cancer cell line, LIV-1 is multispan transmembrane protein of the solute-carrier family 39 with putative zinc transporter and metalloproteinase activity. As downstream target STAT3, it promotes epithelial-to-mesenchymal transition that important malignant progression to metastasis. expressed number cancers highest prevalence level expression breast, prostate, melanoma. Additionally, has been linked metastasis...
Abstract Melanotransferrin (CD228/MFI2/MELTF) is a cell-surfaced glycosylphosphatidylinoitol (GPI)-anchored glycoprotein that belongs to the transferrin family of iron-binding proteins. CD228 was first described as an oncofetal protein highly expressed on malignant melanoma cells. Data from The Cancer Genome Atlas (TCGA) suggests has broad expression across many types carcinomas and it recently potential biomarker invasive colorectal carcinoma. In this study, we characterize using...
Abstract Tucatinib is an investigational, oral, small molecule tyrosine kinase inhibitor that highly selective for the domain of HER2, without significant inhibition EGFR. Recently, HER2CLIMB (NCT02614794), a pivotal, randomized, international, double-blind trial evaluated tucatinib or placebo in combination with trastuzumab and capecitabine patients HER2+ metastatic breast cancer (MBC) brain metastases, after progression trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), showed...
Melanotransferrin (CD228/MFI2/MELTF) is a cell-surfaced glycosylphosphatidylinoitol (GPI)-anchored glycoprotein that belongs to the transferrin family of iron-binding proteins. CD228 was first described as an oncofetal protein highly expressed on malignant melanoma cells. Data from The Cancer Genome Atlas (TCGA) suggests has broad expression across many types carcinomas and it recently potential biomarker invasive colorectal carcinoma. In this study, we characterize using immunohistochemical...