Mesenchymal Stromal Cells: Emerging Roles in Bone Metastasis:Emerging Roles in Bone Metastasis

Bone metastasis is the most advanced stage of many cancers and indicates a poor prognosis for patients due to resistance to anti-tumor therapies. The establishment of metastasis within the bone is a multistep process. To ensure survival within the bone marrow, tumor cells must initially colonize a niche in which they can enter dormancy. Subsequently, reactivation permits the proliferation and growth of the tumor cells, giving rise to a macro-metastasis displayed clinically as a bone metastatic lesion. Here, we review the evidences that suggest mesenchymal stromal cells play an important role in each of these steps throughout the development of bone metastasis. Similarities between the molecular mechanisms implicated in these processes and those involved in the homeostasis of the bone indicate that the metastatic cells may exploit the homeostatic processes to their own advantage. Identifying the molecular interactions between the mesenchymal stromal cells and tumor cells that promote tumor development may offer insight into potential therapeutic targets that could be utilized to treat bone metastasis

Image Synthesis with Disentangled Attributes for Chest X-Ray Nodule Augmentation and Detection

Lung nodule detection in chest X-ray (CXR) images is common to early screening of lung cancers. Deep-learning-based Computer-Assisted Diagnosis (CAD) systems can support radiologists for nodule screening in CXR. However, it requires large-scale and diverse medical data with high-quality annotations to train such robust and accurate CADs. To alleviate the limited availability of such datasets, lung nodule synthesis methods are proposed for the sake of data augmentation. Nevertheless, previous methods lack the ability to generate nodules that are realistic with the size attribute desired by the detector. To address this issue, we introduce a novel lung nodule synthesis framework in this paper, which decomposes nodule attributes into three main aspects including shape, size, and texture, respectively. A GAN-based Shape Generator firstly models nodule shapes by generating diverse shape masks. The following Size Modulation then enables quantitative control on the diameters of the generated nodule shapes in pixel-level granularity. A coarse-to-fine gated convolutional Texture Generator finally synthesizes visually plausible nodule textures conditioned on the modulated shape masks. Moreover, we propose to synthesize nodule CXR images by controlling the disentangled nodule attributes for data augmentation, in order to better compensate for the nodules that are easily missed in the detection task. Our experiments demonstrate the enhanced image quality, diversity, and controllability of the proposed lung nodule synthesis framework. We also validate the effectiveness of our data augmentation on greatly improving nodule detection performance

Interleukin 4 Controls the Pro-Tumoral Role of Macrophages in Mammary Cancer Pulmonary Metastasis in Mice

SIMPLE SUMMARY: Metastasis is the main cause of death from breast cancer. In mouse models of breast cancer lung metastasis, macrophages enhance metastasis by promoting tumor cell seeding and persistent growth. Here, we show that interleukin-4 (IL4) is required for this process as IL4 receptor (IL4rα)-null mice develop fewer and smaller lung metastases. This deficiency is partially rescued by adoptive transfer of wild-type monocytes. IL4 signaling in macrophages upregulates the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. In addition, expression of several other genes already causally associated with lung metastasis including Ccl2, Csf1, Ccr1, Hgf and Flt1 are upregulated in macrophages. High-resolution intravital imaging at the time of metastatic seeding showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages, showing the dependence on IL4. We conclude that IL4 signaling in monocytes and macrophages is important during seeding and growth of breast metastasis in the lung. ABSTRACT: Metastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected transendothelial migration of tumor cells in vitro. Interferon gamma and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα)-null mice developed fewer and smaller lung metastasis in E0771-LG mammary cancer models of this disease. Adoptive transfer of wild-type monocytes to IL4rα-deficient mice partially rescued this phenotype. IL4 signaling in macrophages controlled the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages regulated the transcript abundance of several other genes already causally associated with mammary cancer lung metastasis including Ccl2, Csf1, Ccr1, Hgf and Flt1. The central role of IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages. This interaction with wild-type MAMs enhanced tumor cell survival and seeding, which was lost in the IL4rα mice. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung, as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages

Transitions To the Long-Resident State in coupled chaotic oscillators

The behaviors of coupled chaotic oscillators before complete synchronization were investigated. We report three phenomena: (1) The emergence of long-time residence of trajectories besides one of the saddle foci; (2) The tendency that orbits of the two oscillators get close becomes faster with increasing the coupling strength; (3) The diffusion of two oscillator's phase difference is first enhanced and then suppressed. There are exact correspondences among these phenomena. The mechanism of these correspondences is explored. These phenomena uncover the route to synchronization of coupled chaotic oscillators.Comment: 3 pages, 5 figure