A5014645084- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Bone health and treatments
- Bone Metabolism and Diseases
- Monoclonal and Polyclonal Antibodies Research
- Bone and Dental Protein Studies
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Bone health and osteoporosis research
- RNA modifications and cancer
- Allergic Rhinitis and Sensitization
- Cell death mechanisms and regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Nanoplatforms for cancer theranostics
- Asthma and respiratory diseases
- Cancer Mechanisms and Therapy
- Cancer Diagnosis and Treatment
- Orthopaedic implants and arthroplasty
- Mechanisms of cancer metastasis
- Galectins and Cancer Biology
- Click Chemistry and Applications
- Bone Tissue Engineering Materials
- Metastasis and carcinoma case studies
Vanderbilt University Medical Center
2009-2023
Ablynx (Belgium)
2013-2021
Vanderbilt University
2006-2012
University of Chicago
2010-2011
Centre National de la Recherche Scientifique
2008
Roche (Switzerland)
2008
Abstract Matrix metalloproteinases (MMP) are a family of enzymes with myriad functions. Lately, we have come to realize that broad-spectrum inhibition these enzymes, as was tried unsuccessfully in multiple phase III trials cancer patients, is likely unwise given the protumorigenic and antitumorigenic functions various members. Here, used multistage mammary tumor model MMTV-PyVT investigate roles for either MMP7 or MMP9 progression. We found no effect genetic ablation on multifocal tumors...
Abstract Matrix metalloproteinases (MMPs) are capable of processing certain components bone tissue, including type 1 collagen, a determinant the biomechanical properties and they expressed by osteoclasts osteoblasts. Therefore, we posit that MMP activity can affect ability to resist fracture. To explore this possibility, determined architectural, compositional, bones from wild-type (WT), Mmp2−/−, Mmp9−/− female mice at 16 weeks age. MMP-2 MMP-9 have similar substrates but primarily...
Abstract The matrix metalloproteinases MMP-2, MMP-3, MMP-7, MMP-9, and MMP-13 are highly expressed in the tumor-bone microenvironment, and, of these, MMP-7 MMP-9 were found to be localized bone-resorbing osteoclasts human breast-to-bone metastases. In a bid define roles host-derived tibias null mice injected with osteolytic luciferase–tagged mammary tumor cell lines. Our data show that osteoclast-derived significantly contributes growth tumor-induced osteolysis whereas had no effect on these...
Background Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated resorption and proteolysis results the release of matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis human breast unexpectedly revealed forming osteoblasts were consistently positive for proteinase, MMP-2. Given role MMP-2 extracellular degradation growth factor/cytokine processing, we tested whether osteoblast derived contributed...
Abstract Hypoxia-activated prodrugs (HAP) are a promising class of antineoplastic agents that can selectively eliminate hypoxic tumor cells. This study evaluates the hypoxia-selectivity and antitumor activity CP-506, DNA alkylating HAP with favorable pharmacologic properties. Stoichiometry reduction, one-electron affinity, back-oxidation rate CP-506 were characterized by fast-reaction radiolytic methods observed parameters fulfilling requirements for oxygen-sensitive bioactivation. Net...
Abstract Hypoxia is a characteristic of many solid tumors and defined as low level or absence oxygen due to an insufficient vascularization the tumor transient blockage blood vessels. activates survival response within cells driving cancer progression associated with poor prognosis. Hypoxia-activated prodrugs (HAPs) are anti-neoplastic agents that can solely be activated in hypoxic areas allowing targeted delivery cytotoxic compounds niches. Convert Pharmaceuticals developing CP-506, novel...
Abstract We have developed Cell Penetrating Alphabodies (CPABs), a novel and unique therapeutic class of proteins engineered to efficiently enter cells. In vitro, uptake in range tumor non-tumor cell types occurs rapidly with cytosol levels up 1 μM concentration after 2 hours CPAB exposure. Early forms these CPABs suffered from rapid serum clearance, thereby limiting their efficacy vivo amenability drug development. The incorporation an albumin binding region the body protein has allowed...
The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating antagonist induced myeloid leukemia cell differentiation MCL-1, an target in cancer, by grafting critical B-cell lymphoma 2 homology 3 helix MCL-1 onto tagging scaffold's termini with designed cell-penetration polypeptides. Introduction albumin-binding moiety extended...
Abstract Breast to bone metastases frequently induce a “vicious cycle” in which osteoclast mediated resorption and proteolysis results the release of matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis human breast unexpectedly revealed forming osteoblasts were consistently positive for proteinase, MMP-2. In immunocompetent murine models lytic tumor-bone microenvironment, we identified that, independent function, osteoblast derived...
Abstract Background Hypoxia-activated prodrugs (HAPs) are a promising class of antineoplastic agents that can selectively eliminate hypoxic tumor cells. The present study evaluates the hypoxia-selectivity and antitumor activity CP-506, DNA alkylating HAP with favorable pharmacological properties. Methods Stoichiometry reduction, one-electron affinity, back-oxidation rate CP-506 were characterized by fast-reaction radiolytic methods. In vitro , 2D monolayer 3D spheroid multicellular layer...
Supplementary Figure 1 from Effect of Ablation or Inhibition Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent Genetic Background
Supplementary Figures 1-5 from Osteoclast-Derived Matrix Metalloproteinase-7, but Not Metalloproteinase-9, Contributes to Tumor-Induced Osteolysis
<div>Abstract<p>The matrix metalloproteinases MMP-2, MMP-3, MMP-7, MMP-9, and MMP-13 are highly expressed in the tumor-bone microenvironment, and, of these, MMP-7 MMP-9 were found to be localized bone-resorbing osteoclasts human breast-to-bone metastases. In a bid define roles host-derived tibias null mice injected with osteolytic luciferase–tagged mammary tumor cell lines. Our data show that osteoclast-derived significantly contributes growth tumor-induced osteolysis whereas had...
<div>Abstract<p>Matrix metalloproteinases (MMP) are a family of enzymes with myriad functions. Lately, we have come to realize that broad-spectrum inhibition these enzymes, as was tried unsuccessfully in multiple phase III trials cancer patients, is likely unwise given the protumorigenic and antitumorigenic functions various members. Here, used multistage mammary tumor model MMTV-PyVT investigate roles for either MMP7 or MMP9 progression. We found no effect genetic ablation on...
Supplementary Figure Legend from Effect of Ablation or Inhibition Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent Genetic Background
Supplementary Figure 1 from Effect of Ablation or Inhibition Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent Genetic Background
Supplementary Figure Legend from Effect of Ablation or Inhibition Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent Genetic Background
<div>Abstract<p>Matrix metalloproteinases (MMP) are a family of enzymes with myriad functions. Lately, we have come to realize that broad-spectrum inhibition these enzymes, as was tried unsuccessfully in multiple phase III trials cancer patients, is likely unwise given the protumorigenic and antitumorigenic functions various members. Here, used multistage mammary tumor model MMTV-PyVT investigate roles for either MMP7 or MMP9 progression. We found no effect genetic ablation on...