Johns Hopkins Physical science Oncology Center

Hopkins, United States

Johns Hopkins Physical science Oncology Center

Hopkins, United States
SEARCH FILTERS
Time filter
Source Type

Wang P.,Northeastern University China | Wang P.,University of Connecticut | Guan P.-P.,Northeastern University China | Guan P.-P.,University of Connecticut | And 6 more authors.
FASEB Journal | Year: 2013

The mechanical overloading of cartilage is involved in the pathophysiology of osteoarthritis (OA) by both biochemical and mechanical pathways. The application of fluid shear stress to chondrocytes recapitulates the earmarks of OA, as evidenced by the release of proinflammatory cytokines (PICs), matrix metalloproteinases (MMPs), and apoptotic factors. Dysregulations or mutations in these genes might directly cause OA in addition to determining the stage at which OA becomes apparent, the joint sites involved, and the severity of the disease and how rapidly it progresses. However, the underlying mechanisms remain unknown. In this review, we propose that the dysregulation of cyclooxygenase-2 (COX-2) is associated with fluid shear stress-induced OA via its metabolic products at different stages of the disease. Indeed, high fluid shear stress rapidly induces the production of PICs and MMPs via COX-2-derived prostaglandin (PG)E2 at the early stage of OA. In contrast, prolonged shear exposure (>12 h) aggravates the condition by concurrently up-regulating the expression of proapoptotic genes and down-regulating the expression of antiapoptotic genes in a 15-deoxy- (12,14)-prostaglandin J2 (15d-PGJ2)-dependent manner at the late stage of disease. These observations may help to resolve long-standing questions in OA progression and provide insight for development of strategies to treat and combat OA.-Wang, P., Guan, P.-P., Guo, C., Zhu, F., Konstantopoulos, K., Wang, Z.-W. Fluid shear stressinduced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases. © FASEB.


Gilkes D.M.,Institute for Cell Engineering | Gilkes D.M.,McKusick Nathans Institute of Genetic Medicine | Gilkes D.M.,Johns Hopkins Physical science Oncology Center | Chaturvedi P.,Institute for Cell Engineering | And 17 more authors.
Cancer Research | Year: 2013

The presence of hypoxia and fibrosis within the primary tumor are two major risk factors for metastasis of human breast cancer. In this study, we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced invasion and metastasis to lymph nodes and lungs. Finally, we establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast cancer. © 2013 American Association for Cancer Research.


Gilkes D.M.,Institute for Cell Engineering | Gilkes D.M.,McKusick Nathans Institute of Genetic Medicine | Gilkes D.M.,Johns Hopkins Physical science Oncology Center | Bajpai S.,Johns Hopkins Physical science Oncology Center | And 13 more authors.
Molecular Cancer Research | Year: 2013

Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix (ECM) in the metastatic process may lead to the development of improved therapies to treat patients with cancer. Intratumoral hypoxia, found in the majority of breast cancers, is associated with an increased risk of metastasis and mortality. We found that in hypoxic breast cancer cells, hypoxia-inducible factor 1 (HIF-1) activates transcription of the PLOD1 and PLOD2 genes encoding procollagen lysyl hydroxylases that are required for the biogenesis of collagen, which is a major constituent of the ECM. High PLOD2 expression in breast cancer biopsies is associated with increased risk of mortality. We show that PLOD2 is critical for fibrillar collagen formation by breast cancer cells, increases tumor stiffness, and is required for metastasis to lymph nodes and lungs. Copyright © 2013 American Association for Cancer Research.


Kusuma S.,Johns Hopkins Physical science Oncology Center | Kusuma S.,Johns Hopkins University | Gerecht S.,Johns Hopkins Physical science Oncology Center
Expert Review of Cardiovascular Therapy | Year: 2010

Vascular disease is the leading cause of mortality in the USA, providing the impetus for new treatments and technologies. Current therapies rely on the implantation of stents or grafts to treat injured blood vessels. However, these therapies may be immunogenic or may incompletely recover the functional integrity of the vasculature. In light of these shortcomings, cell-based therapies provide new treatment options to heal damaged areas with more suitable substitutes. Current clinical trials employing stem cell-based therapies involve the transfusion of harvested endothelial progenitor cells. While the results from these trials have been encouraging, utilizing tissue-engineered approaches could yield technologically advanced solutions. This article discusses engineered stem cell-based therapies from three angles: the differentiation of adult stem cells, such as mesenchymal stem cells and endothelial progenitor cells, into vascular lineages; investigation of human embryonic stem cells and induced pluripotent stem cells as inexhaustible sources of vascular cells; and tissue-engineering approaches, which incorporate these vascular progenitor cells into biomimetic scaffolds to guide regeneration. The optimal solution to vascular disease lies at the interface of these technologies - embedding differentiated cells into engineered scaffolds to impart precise control over vascular regeneration. © 2010 Expert Reviews Ltd.

Loading Johns Hopkins Physical science Oncology Center collaborators
Loading Johns Hopkins Physical science Oncology Center collaborators