A review of current murine models of multiple myeloma used to assess the efficacy of therapeutic agents on tumour growth and bone disease

Bone ◽  
2015 ◽  
Vol 77 ◽  
pp. 57-68 ◽  
Author(s):  
J. Paton-Hough ◽  
A.D. Chantry ◽  
M.A. Lawson
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Tumour Growth ◽  
Therapeutic Agents ◽  
Murine Models

The effect of the dual PI3K and mTOR inhibitor BEZ235 on tumour growth and osteolytic bone disease in multiple myeloma

2014 ◽  
Vol 94 (4) ◽  
pp. 343-354 ◽  
Author(s):  
Zhen Ying Gan ◽  
Stephen Fitter ◽  
Kate Vandyke ◽  
Luen B. To ◽  
Andrew C.W. Zannettino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Tumour Growth ◽  
Mtor Inhibitor ◽  
Osteolytic Bone Disease

The effect of the PI3K inhibitor BKM120 on tumour growth and osteolytic bone disease in multiple myeloma

2015 ◽  
Vol 39 (3) ◽  
pp. 380-387 ◽  
Author(s):  
Sally K. Martin ◽  
Zhen Ying Gan ◽  
Stephen Fitter ◽  
Luen B. To ◽  
Andrew C.W. Zannettino
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Tumour Growth ◽  
Pi3k Inhibitor ◽  
Osteolytic Bone Disease

A Novel Murine Model of Human Disseminated Multiple Myeloma with A Subcutaneous Human Bone Chip from an Adult Donor Confers Proliferative Advantage and Is Suitable for the In Vivo Evaluation of Novel Drugs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4077-4077
Author(s):  
Enrique M. Ocio ◽  
Laura San-Segundo ◽  
Juan Blanco ◽  
Teresa Hernández-Iglesias ◽  
Diego Fernández-Lázaro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Murine Model ◽  
Tumour Growth ◽  
Luciferase Activity ◽  
Human Bone ◽  
Murine Models ◽  
Bone Chip ◽  
Novel Drugs ◽  
Novel Model

Abstract Abstract 4077 Several murine models resembling multiple myeloma have been developed in the last years: the subcutaneous plasmocytoma model and the disseminated model, based on the iv or intracardiac injection of MM cells, have been widely used to test the efficacy of novel agents. Nevertheless, it is well known the crucial role that the interaction between MM plasma cells and the bone marrow microenvironment plays in MM pathogenesis as well as in the proliferation of MM cells and drug resistance; however, unfortunately, most murine models do not recapitulate these interactions. In order to overcome this caveat, other models such as the SCIDhu or the SCIDrab have been developed. However, in these models, the induced microenvironmental milleu is derived from a fetus and a rabbit respectively, which can be relatively different from that found in an adult patient with MM. We have developed a novel model of a human disseminated MM with the presence of human adult microenvironment. For this purpose, CB17-SCID mice, which lack B and T lymphocytes, were anesthetized and a human bone chip obtained from a healthy adult patient undergoing a hip replacement due to a non-malignant fracture, was subcutaneously implanted in the back of the mice. In the same day 3×106 MM1S-Luc cells were iv injected through the tail vein. Two groups were also included as controls in the study, one with MM1S-Luc cells without the bone chip, and the other with only the human bone chip (without MM cells). Luciferase activity was measured three times per week using a Xenogen-IVIS 50 system after ip injection of 0,15 mg/Kg luciferin. Mice were sacrificed when they developed signs associated with advanced disease, such as body weight loss or back limb paralysis. Although the group of mice receiving MM1S-Luc without bone, did develop a disseminated myeloma, this was much more precocious in the group of mice with a human bone subcutaneous implant. In fact, in mice with human bone and MM1S-Luc cells, the luciferase activity was detectable a median of 9 days after the injection of the cells whereas it was necessary 16 days for obtaining the same effect in mice without the bone chip. This is pointing out that the bone chip in these mice induces a favourable environment for myeloma growth and could be appropriate model to study the interactions of MM cells with human stroma. The increase of tumour growth rate also correlated with a decrease in survival. Median survival (CI 95%) of 64 (47-80) days for mice without bone vs 48 (45-50) days for mice with human bone (Log Rank=0.004). Regarding the sites of infiltration, luminescence images showed a disseminated involvement in all skeletal regions, and this was confirmed by histopathology, as there was a general infiltration of spine, femora, tibia and cranium of these mice. By contrast we did not find infiltration of extra-skeletal regions such as heart, lung or spleen in any mice and only unclear infiltrates were observed in the kidney and liver of some mice. In order to validate the suitability of this model for testing the in vivo antimyeloma activity of novel drugs in the presence of a human microenvironment, 6 mice bearing this novel model were randomized to receive: bortezomib (0.5 mg/Kg ip five days per week) + dexamethasone (0.5 mg/Kg 2 days per week) or vehicle control. A second group of the same number of mice with MM1S-Luc but without the bone chip were randomized in the same way and used as control. Bortezomib + dex significantly decreased tumour growth in both groups of mice without any clear differences in activity between both models, suggesting that this combination overcomes the influence of the microenvironment. In summary we have developed a murine model of MM that may allows us to 1) gain insights into the role of the BM microenvironment interactions in MM pathogenesis. 2) Evaluate the in vivo activity of different anti-MM agents in the presence of human microenvironment. 3) Potentially, this model could also contribute to analyze the effect of different agents in the myeloma bone disease. Disclosures: No relevant conflicts of interest to declare.

Involvement of LIGHT in multiple myeloma bone disease

2014 ◽  
Author(s):  
Angela Oranger ◽  
Giacomina Brunetti ◽  
Giorgio Mori ◽  
Claudia Carbone ◽  
Isabella Gigante ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Myeloma Bone Disease

Anti-sclerostin treatment prevents multiple myeloma bone disease and reduces tumour burden

2016 ◽  
Author(s):  
Michelle McDonald ◽  
Michaela Reagan ◽  
Rachael Terry ◽  
Jessica Pettitt ◽  
Lawrence Le ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Tumour Burden ◽  
Myeloma Bone Disease

Contribution of multiple myeloma-derived exosomes to bone disease

2016 ◽  
Author(s):  
Lavinia Raimondi ◽  
Luca Angela De ◽  
Valeria Carina ◽  
Valentina Agnese ◽  
Simona Fontana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

Impact of Natural Dietary Agents on Multiple Myeloma Prevention and Treatment: Molecular Insights and Potential for Clinical Translation

2020 ◽  
Vol 27 (2) ◽  
pp. 187-215 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Gianluca Giavaresi ◽  
Agnese Barone ◽  
Pierosandro Tagliaferri ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Multiple Myeloma ◽  
Natural Products ◽  
Bone Disease ◽  
Molecular Mechanisms ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
Signal Transduction Pathways ◽  
Pharmacologically Active ◽  
Dietary Agents

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.

Sign in / Sign up

Export Citation Format

Share Document