| Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis |
Sep 2012 |
8 pages |
| Authors:
Selvarangan Ponnazhagan; CALIFORNIA UNIV BERKELEY
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 | Bone is the most common site of metastasis for human breast cancer (BCa), which results in significant morbidity and mortality in patients with advanced disease. A vicious cycle, arising due to the interaction of BCa cells and cells in the bone microenvironment results in the activation of osteoclasts and increased osteolytic bone destruction. The major treatment to reduce the burden of bone metastasis in BCa patients is bisphosphonate therapy. Despite ... |
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| Transforming Growth Factor Beta Signaling in Growth of Estrogen-Insensitive Metastatic Bone Lesions |
Jan 2012 |
99 pages |
| Authors:
Nicole Nickerson; INDIANA UNIV INDIANAPOLIS
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| While many women with breast cancer will use estrogen receptor therapeutics such as fulvestrant, resistance is nearly inevitable. Recently, it has been noted that the epidermal growth factor receptor (EGFR) family plays a vital role in metastasis to bone; also cross signaling with the transforming growth factor receptor type II (TGFBR2) has been noted to increase levels of destructive environmental cytokines. Therefore we are examining the role of EGFR/TGFBR2 cross ... |
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| A New In Vitro Model of Breast Cancer Metastasis to Bone |
Apr 2009 |
159 pages |
| Authors:
Andrea M Mastro; Erwin A Vogler; Carol V Gay; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
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| Breast cancer frequently metastasizes to the bone where it disrupts the balance between osteoblasts and osteoclasts and leads to osteolytic degradation. The objective of this study was to test the hypothesis that osteolytic bone metastases results partly from the effect of the cancer cells on the osteoblasts, i.e., the cancer cells prevent osteoblasts from accreting mineralized tissue, ultimately leading to accelerated skeletal degradation. To test this idea, we proposed to ... |
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| How MMPs Impact Bone Responses to Metastatic Prostate Cancer |
FEB 2008 |
10 pages |
| Authors:
Conor C. Lynch; VANDERBILT UNIV NASHVILLE TN
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| Using an animal model of prostate tumor progression in the bone we have previously shown that MMPs, namely MMP-2,-3,-9 and -13, are overexpressed at the tumor bone interface and these MMPs are for the most part expressed by the host cells of the bone. To test the contribution of MMPs in prostate tumor progression in the bone, we have generated mice that are immunocompromized and deficient for MMP-2,-3 and -9 ... |
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| Systemic and Gene Modified Mesenchymal Stem Cell Therapy for Metastatic Prostate Cancer |
MAY 2007 |
7 pages |
| Authors:
Selvarangan Ponnazhagan; ALABAMA UNIV IN BIRMINGHAM
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| Bone is the frequent metastatic site for human prostate cancer resulting in significant morbidity and mortality in patients with advanced disease. The type of bone defect encountered in prostate cancer bone metastasis is osteoblast lesions resulting in excess bone. However, initiation of osteoclastogenesis is first aided by osteolysis, mediated by osteoclasts. The areas provided as source for osteoblast accumulation later leads to thickening of the bone. In this proposal, we ... |
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| Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases |
01 MAR 2007 |
28 pages |
| Authors:
Sarah A. Arrington; Matthew J. Allen; Timothy A. Damron; Kenneth A. Mann; SYRACUSE UNIV RESEARCH FOUNDATION NY
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| The skeleton is the most common site of metastasis for women with advanced stage breast cancer (5, 8, 22). Severe osteolysis that is often associated with this stage of the disease can lead to skeletal related events such as pathological fracture severe bone pain and hypocalcaemia. The current standard of care for treating osteolytic bone metastases includes palliating bone pain through radiation therapy and blocking ongoing osteoclastic bone resorption with ... |
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| Trafficking of Metastatic Breast Cancer Cells in Bone |
AUG 2006 |
27 pages |
| Authors:
Andrea M. Mastro; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
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| Breast cancer metastases are usually found at the ends (metasphyses) of long bones where they cause osteolysis. The objective was to determine the trafficking of cancer cells in the marrow cavity and to identify factors that attract them. Human breast cancer cells that express green fluorescent protein (MDAMB 231GFP) were inoculated intracardiacly into athymic mice.; femurs harvested from 1 hr to 6 wk later and analyzed by fluorescence microscopy, immunohistochemistry, ... |
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| Transforming Growth Factor Beta Regulation of Tumor Progression in Metastatic Cancer |
JUN 2004 |
138 pages |
| Authors:
Merry Jo Oursler; MINNESOTA UNIV MINNEAPOLIS
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| During the metastatic tumor development, osteoclasts differentiate in the presence of high transforming growth factor beta (TGF-beta) concentrations. We hypothesize that TGF-beta is a survival factor for TGF-beta-induced osteoclasts. We tested our hypothesis by: (l) Determining the effects of TGF- beta on tumor development in bone in vivo and (2) Determining the role of TCF- beta signal transduction in TGF-beta influences on mouse osteoclasts-like cell survival. We have compared mice ... |
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| PSA Converts Parathyroid Hormone-Related Protein (PTHrP) from an Osteolytic to an Osteoblastic Factor: Role in Bone Metastasis |
DEC 2003 |
19 pages |
| Authors:
John M. Chirgwin; VIRGINIA UNIV CHARLOTTESVILLE
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| Prostate cancer metastases cause disorganized new bone formation, despite expressing the bone- destructive factor, PThrP. We report a molecular basis for this paradox: residues 6-9 LMDK of ET- 1 and PTHrP residues 8-11 LHDK share sequence similarity. PTHrP is cleaved at residues 22 and 23 by the serine protease, prostate-specific antigen (PSA). The fragments generated by PSA are too short to activate the PTH1 receptor but stimulate new bone by ... |
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| Breast Tumor/Stromal Cell Interactions in Bone |
JUL 2003 |
29 pages |
| Authors:
Normand Pouliot; Robin L. Anderson; PETER MACCALLUM CANCER INST MELBOURNE (AUSTRALIA)
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| We are investigating interactions between breast cancer and bone stromal cells and their role in regulating metastasis of breast tumor cells to bone and osteoclast development using an orthotopic mouse model. Results from in vivo experiments indicate that PTHrP is an important factor regulating tumor growth but is not required for specific metastasis of breast tumors to bone. In vitro co-culture of bone stromal and tumor cells leads to up-regulation ... |
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| The Role of Estrogen Receptor-Alpha in Breast Cancer Metastases to Bone |
SEP 2002 |
15 pages |
| Authors:
Theresa A. Guise; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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| Breast cancer osteolysis is common and the morbidity is devastating. The consequences of intractable bone pain, fracture, hypercalcemia and nerve compression syndromes are debilitating and the tumor is incurable once it has metastasized to bone. Women with bone metastases live many years with this incurable complication and are at high risk for morbidity. A more aggressive approach to prevent and treat bone metastases is a necessary addition to the standard ... |
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| Breast Tumor/Stromal Cell Interactions in Bone |
JUL 2002 |
14 pages |
| Authors:
Michael D. Tavaria; Robin L. Anderson; PETER MACCALLUM CANCER INST MELBOURNE (AUSTRALIA)
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| Metastasis to bone is a common and serious complication of breast cancer. The aim of this project is to use our unique mouse model of breast cancer metastasis to bone to identify the molecular basis for this problem. In the first year, we have investigated the expression of a panel of candidate genes in tumor cells that metastasize to bone compared to those that do not metastasize or that metastasize ... |
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| Viability of Bone Cement Augmented Compression HIP Screw System for The Treatment of Intertrochanteric Fracture: A Biomechanical Analysis |
25 OCT 2001 |
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| Authors:
S. J. Lee; B. J. Kim; S. Y. Kwon; J. W. Shin; G. R. Tack; INJE UNIV KIMHAE (KOREA) DEPT OF BIOMEDICAL ENGINEERING
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 | Screw cut-out and non-union have been cited as major complications with hip screw systems for the treatment of intertrochanteric femoral fractures. Recently, cement augmentation of hip screw system has been introduced to provide better purchase of the screw. This study investigates the biomechanical efficacy of cement augmentation technique by assessing the changes in stress distributions within the femur and the surgical construct. Finite element models of the operated femur with ... |
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| Mechanisms for Controlling Breast Cancer Growth and Skeletal Metastasis |
JUN 2001 |
31 pages |
| Authors:
Nandini Ghosh-Choudhury; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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| Bone morphogenetic protein-2 (BMP-2), an osteoblastic growth and differentiation factor is found to inhibit estradiol- stimulated growth of estrogen receptor (ER) containing MCF7 human breast cancer cells as well as the ER negative but EGF-responsive growth of MDA MB 231 cells. The underlying mechanism for growth inhibition by BMP-2 involved inhibition in retinoblastoma protein (pRb) phosphorylation, which is essential for the cells to proliferate. We also demonstrated that BMP-2 inhibits ... |
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| Cathepsins B and K: Role in Metastasis of Human Prostate Cancer to Human Bone in an In Vivo SCID-hu Mouse Model |
MAR 2001 |
30 pages |
| Authors:
Bonnie F. Sloane; WAYNE STATE UNIV DETROIT MI
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| Cathepsins K and B have been implicated in bone resorption in several pathologies. Expression of cathepsin B is highly upregulated in human prostate cancer. Cathepsin K, in contrast to cathepsin B, is expressed predominantly in osteoclasts. Cathepsin K has recently been identified in tumor cells within human breast tumor bone metastases and in adjacent osteoclasts, suggesting that cathepsin K may participate in bone resorption by tumor cells. Therefore, we are ... |
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| Bone Factors Regulating the Osteotropism of Metastastic Breast Cancer |
OCT 2000 |
34 pages |
| Authors:
Peter V. Hauschka; CHILDREN'S HOSPITAL CORP BOSTON MA
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| Malignant breast adenocarcinoma cells mimic osteoblasts, a critical step in their metastatic colonization and destruction of bone. CBFAl, a transcription factor responsible for normal osteoblast differentiation, is expressed inappropriately by the human breast adenocarcinoma cell line MDA-MB-23 1, and about 2-fold more strongly by a subline Ml, recovered from an osteolytic bone metastasis of MDA-MB-23 1 in a nu/nu mouse. CBFAl expression was not detected in normal breast epithelium (HMEC ... |
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| Breast Cancer Stimulation of Osteolysis |
SEP 2000 |
48 pages |
| Authors:
Merry J. Oursler; MINNESOTA UNIV DULUTH
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| In the three years of funding, we have completed analysis of two tumors and have found mRNA and protein for GM-C SF, IGF-I and II, PThrP, and TNF-alpha. We have also studied a mouse model for metastatic tumor development and determined that there is variable filming of the appearance of tumor-derived factors during tumor development. We have examined these factors for their effects on apoptosis and found that TNF-alpha, but ... |
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| The Role of Parathyroid Hormone-Related Protein in Breast Cancer Mediated Osteolysis |
OCT 1999 |
112 pages |
| Authors:
Theresa Gruise; TEXAS UNIV AT SAN ANTONIO
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| Breast cancer affects the skeleton through humoral and local osteolytic mechanisms to cause the devastating complications of hypercalcemia, pain, fracture and nerve compression syndromes. PTHrP mediates hypercalcemia through its systemic effects to increase osteoclastic bone resorption as well as renal tubular calcium reabsorption in at least 50% of hypercalcemic breast cancer patients even in the presence of bone metastases. Due to this potent bone resorbing capacity, ... |
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| Role of Parathyroid Hormone-Related Protein in Breast Cancer Mediated Osteolysis |
OCT 1998 |
29 pages |
| Authors:
Theresa A. Guise; TEXAS UNIV AT SAN ANTONIO
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| The purpose of this study is to define the role of PTHrP in the pathophysiology of breast cancer using animal models of breast cancer-mediated humoral hypercalcemia and osteolytic bone metastases. Our previous studies reported in the first 3 years of this proposal indicate that 50% of breast cancer cell lines tested secrete low, but significant amounts of PTHrP. Over- expression of PTHrP-(1-141) in the human breast cancer cell line, MDA-MB-231, ... |
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| Role of Bone Sialoproteins in Osseous Metastasis of Breast Cancer |
JUL 97 |
64 pages |
| Authors:
Victoria Sung; GEORGETOWN UNIV WASHINGTON DC
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| The ability of certain human breast cancer cells (HBC) to metastasize to bone may be related to cellular expression of the small acidic sialoproteins osteopontin (OPN) and bone sialoprotein (BSP). Expression of these proteins may promote primary tumor cell invasion, and/or the development of bone metastases. The purpose of this study is to compare BSP and OPN expression in HBC to bone metastatic potential and to examine potential breast cancer ... |
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| Role of Parathyroid Hormone-Related Protein in Breast Cancer Mediated Osteolysis |
OCT 96 |
35 pages |
| Authors:
Theresa A. Guise; TEXAS UNIV AT SAN ANTONIO
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| This proposal is designed to investigate the role of PTHrP in breast cancer-mediated osteolysis. Observations in patients with bone metastases suggest that breast cancer cells in bone express PTHrP more frequently than in soft tissue sites of metastasis or in the primary tumor. Thus, the role of PTHrP in the causation of breast cancer metastases in bone was examined using human breast cancer cell lines. Four of eight breast cancer ... |
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