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Related Concept Videos

Growth of Cartilage and Bone Tissue01:27

Growth of Cartilage and Bone Tissue

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Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
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Spongy Bone01:09

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All bones comprise an outer layer of compact bone, and an interior made up of spongy bone tissue, also called cancellous or trabecular bone. In long bones, spongy bone tissue is mainly found in the interior of the epiphyses (broad ends of the bone).
Spongy bone is more porous, and less dense compared to compact bone. It is composed of concentric lamellae that are arranged irregularly to form the trabecular network. In some bones, the spaces between trabeculae contain red marrow, where...
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Compact Bone01:27

Compact Bone

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Most bones contain compact and spongy osseous tissue, but their distribution and concentration vary based on the bone's overall function.
Compact bone, also called cortical bone, is the denser, stronger of the two types of bone tissue. It is found under the periosteum and in the diaphyses of long bones, where it provides support and protection. The microscopic structural unit of compact bone is called an osteon, or haversian system. Each osteon is composed of concentric rings of calcified...
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Bone Disorders01:29

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Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
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The Hyoid Bone01:12

The Hyoid Bone

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The hyoid bone is a small U-shaped bone located in the upper neck at the level of the inferior mandible, with its tips pointing posteriorly. It does not directly articulate with any other bone in the body. The hyoid acts as the attachment site for the tongue, the larynx, and the pharynx. It is held in position by a series of small muscles attached from above or below. These muscles help to move the hyoid up/down or forward/back in coordination with movements of the tongue, larynx, and pharynx...
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Bone Structure01:55

Bone Structure

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Within the skeletal system, the structure of a bone, or osseous tissue, can be exemplified in a long bone, like the femur, where there are two types of osseous tissue: cortical and cancellous.
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Models of Bone Metastasis
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Human Immune System Increases Breast Cancer-Induced Osteoblastic Bone Growth in a Humanized Mouse Model without

Tiina E Kähkönen1, Mari I Suominen1, Jenni H E Mäki-Jouppila1

  • 1Pharmatest Services, Turku 20520, Finland.

Journal of Immunology Research
|June 19, 2019
PubMed
Summary

This study establishes a novel humanized mouse model for studying breast cancer bone metastases. The model demonstrates increased tumor growth and bone changes, aiding in the evaluation of new immuno-oncology therapies.

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Area of Science:

  • Oncology
  • Immunology
  • Preclinical Models

Background:

  • Bone metastases are common in breast, prostate, and lung cancers, necessitating new therapeutic strategies.
  • Human immune system-engrafted models are crucial for immuno-oncology (IO) research, but models for bone metastases are lacking.
  • Developing novel efficacy models for IO compounds targeting bone metastases is essential.

Purpose of the Study:

  • To characterize a new breast cancer bone metastasis model using humanized mice (huNOG).
  • To evaluate the utility of this model for assessing novel immuno-oncology therapies.
  • To analyze tumor-induced bone changes and the tumor microenvironment.

Main Methods:

  • Human CD34+ hematopoietic stem cells were engrafted into NOG mice (huNOG).
  • BT-474 human breast cancer cells were inoculated into the tibia bone marrow.
  • Bone phenotyping, imaging (X-ray, micro-CT), and immunohistochemistry were performed.

Main Results:

  • huNOG mice exhibited osteoblastic bone growth, earlier and larger bone lesions, and increased bone mineral density.
  • BT-474 tumors were characterized as "cold" tumors with low tumor-infiltrating lymphocytes (TILs) and immune checkpoint expression.
  • huNOG mice showed robust human immune cell engraftment in immune organs.

Conclusions:

  • The study successfully characterized the first breast cancer bone growth model in huNOG mice.
  • This model provides a valuable platform for evaluating combination therapies, including IO agents, for bone metastatic breast cancer.
  • The BT-474 model's "cold" tumor characteristics are suitable for testing immune-stimulatory approaches.