Abstract 709: Anti-PD-1 therapy reduces bone lesion growth in a novel syngeneic bladder cancer bone metastasis model

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Non-invasive imaging techniques have been recently developed to characterize animal models of disease. The overarching hypothesis of this work explores the use of three micro-imaging modalities, including Micro-CT, PET and SPECT, to characterize tumor anatomical progression, metabolism, bone lesion remodeling, and/or gastrin releasing peptide receptor expression in mouse models of metastatic melanoma and prostate and breast cancer bone metastasis. Micro-CT was shown to provide excellent anatomical information about tumor progression in several different tissues including lung, bone, and subcutaneous tissues. Micro-PET imaging demonstrated increased tumor metabolism in melanoma tumors, but was not able to discern bone remodeling in breast cancer bone lesions. Micro-SPECT imaging demonstrated gastrin-releasing peptide receptor expression in a prostate cancer bone metastasis model. The results from this work demonstrate the ability of micro-imaging technologies to non-invasively probe mouse models of disease to obtain information in vivo that is not possible with ex vivo experimental techniques.

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Two cases of osteoblastic bone metastasis from muscle-invasive bladder cancer with discrepancy in response to chemotherapy: problems and limitations of bone biopsy

International Cancer Conference Journal ◽

10.1007/s13691-020-00435-1 ◽

2020 ◽

Vol 9 (4) ◽

pp. 235-239

Author(s):

Takuto Ogasawara ◽

Toshiaki Tanaka ◽

Tetsuya Shindo ◽

Kohei Hashimoto ◽

Fumimasa Fukuta ◽

...

Keyword(s):

Bladder Cancer ◽

Bone Metastasis ◽

Bone Biopsy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Response To Chemotherapy ◽

Muscle Invasive

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Conditional Knockdown of Osteopontin Inhibits Breast Cancer Skeletal Metastasis

International Journal of Molecular Sciences ◽

10.3390/ijms20194918 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4918 ◽

Cited By ~ 6

Author(s):

Marineta Kovacheva ◽

Michael Zepp ◽

Muriel Schraad ◽

Stefan Berger ◽

Martin R. Berger

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Skeletal Metastasis ◽

Skeletal Metastases ◽

Specific Gene ◽

Cell Clones ◽

Gene And Protein Expression ◽

Metastasis Model ◽

Breast Cancer Bone Metastasis

High osteopontin (OPN) expression is linked to breast cancer bone metastasis. In this study we modulated osteopontin levels conditionally and investigated any related antineoplastic effects. Therefore, we established cell clones from human breast cancer MDA-MB-231 cells, in which the expression of OPN is regulated by the Tet-Off tet-off system. These cells, which conditionally express a specific miRNA targeting OPN, were used for in vitro studies as well as for a bone metastasis model in nude rats. Changes in whole-genome expression elicited by conditional OPN knockdown and vesicle formation were also analyzed. The alkylphosphocholine erufosine was used for combination therapy. Conditional OPN knockdown caused mild anti-proliferative, but more intensive anti-migratory and anti clonogenic effects, as well as partial and complete remissions of soft tissue and osteolytic lesions. These effects were associated with specific gene and protein expression modulations following miRNA-mediated OPN knockdown. Furthermore, high levels of OPN were detected in vesicles derived from rats harboring breast cancer skeletal metastases. Finally, the combination of OPN inhibition and erufosine treatment caused an additive reduction of OPN levels in the investigated breast cancer cells. Thus, knockdown of OPN alone or in combination with erufosine is a promising strategy in breast cancer skeletal metastasis treatment.

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