ORCID Profile
0000-0001-7879-7708
Current Organisations
Walter and Eliza Hall Institute of Medical Research
,
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 07-10-2014
DOI: 10.1038/LEU.2014.295
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-8997-3_20
Abstract: Multiple myeloma (MM) is a plasma cell neoplasm which is defined by strong interactions with the bone marrow microenvironment, a compartment with high cellular heterogeneity and unique structural and extracellular components. This necessitates the use of in vivo models for research to fully recapitulate MM growth conditions. The selection of appropriate model system is crucial, as each has advantages and shortcomings. Here, we describe the murine models available for studying MM, and focus on the methods for inoculating mice with MM cells via intravenous, intratibial or subcutaneous delivery, as well as monitoring of disease and organ processing for further analysis. The interaction and destruction of bone is a hallmark symptom of MM, and therefore many other complementary techniques used in calcified tissue research can be used, such as microCT, histomorphometry, and biomechanical testing.
Publisher: American Association for Cancer Research (AACR)
Date: 13-03-2014
DOI: 10.1158/0008-5472.CAN-13-2645
Abstract: The bone marrow provides a specialized and highly supportive microenvironment for tumor growth and development of the associated bone disease. It is a preferred site for breast and prostate cancer bone metastasis and the hematologic malignancy, multiple myeloma. For many years, researchers have focused upon the interactions between tumor cells and the cells directly responsible for bone remodeling, namely osteoclasts and osteoblasts. However, there is ever-increasing evidence for a multitude of ways in which the bone marrow microenvironment can promote disease pathogenesis, including via cancer-associated fibroblasts, the hematopoietic stem cell niche, myeloid-derived suppressor cells, and the sympathetic nervous system. This review discusses the recent advances in our understanding of the contribution of the host microenvironment to the development of cancer-induced bone disease. Cancer Res 74(6) 1625–31. ©2014 AACR.
Publisher: Springer Science and Business Media LLC
Date: 02-10-2019
DOI: 10.1038/S41598-019-50591-5
Abstract: Interactions between multiple myeloma (MM) and bone marrow (BM) are well documented to support tumour growth, yet the cellular mechanisms underlying pain in MM are poorly understood. We have used in vivo murine models of MM to show significant induction of nerve growth factor (NGF) by the tumour-bearing bone microenvironment, alongside other known pain-related characteristics such as spinal glial cell activation and reduced locomotion. NGF was not expressed by MM cells, yet bone stromal cells such as osteoblasts expressed and upregulated NGF when cultured with MM cells, or MM-related factors such as TNF-α. Adiponectin is a known MM-suppressive BM-derived factor, and we show that TNF-α-mediated NGF induction is suppressed by adiponectin-directed therapeutics such as AdipoRON and L-4F, as well as NF-κB signalling inhibitor BMS-345541. Our study reveals a further mechanism by which cellular interactions within the tumour-bone microenvironment contribute to disease, by promoting pain-related properties, and suggests a novel direction for analgesic development.
Publisher: Public Library of Science (PLoS)
Date: 07-09-2012
Publisher: Springer Science and Business Media LLC
Date: 04-10-2019
DOI: 10.1038/S41467-019-12296-1
Abstract: Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts bone homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced bone destruction are poorly understood and current therapies do not restore lost bone mass. Using transcriptomic profiling of isolated bone lining cell subtypes from a murine myeloma model, we find that bone morphogenetic protein (BMP) signalling is upregulated in stromal progenitor cells. BMP signalling has not previously been reported to be dysregulated in myeloma bone disease. Inhibition of BMP signalling in vivo using either a small molecule BMP receptor antagonist or a solubilized BMPR1a-FC receptor ligand trap prevents trabecular and cortical bone volume loss caused by myeloma, without increasing tumour burden. BMP inhibition directly reduces osteoclastogenesis, increases osteoblasts and bone formation, and suppresses bone marrow sclerostin levels. In summary we describe a novel role for the BMP pathway in myeloma-induced bone disease that can be therapeutically targeted.
Publisher: Springer Science and Business Media LLC
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 26-08-2019
DOI: 10.1038/S41598-019-48841-7
Abstract: Experimental biological model system outcomes such as altered animal movement capability or behaviour are difficult to quantify manually. Existing automatic movement tracking devices can be expensive and imposing upon the typical environment of the animal model. We have developed a novel multiplatform, free-to-use open-source application based on OpenCV, called AnimApp. Our results show that AnimApp can reliably and reproducibly track movement of small animals such as rodents or insects, and quantify parameters of action including distance and speed in order to detect activity changes arising from handling, environment enrichment, or temperature alteration. This system offers an accurate and reproducible experimental approach with potential for simple, fast and flexible analysis of movement and behaviour in a wide range of model systems.
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Sam Olechnowicz.